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| ID | Type | Description | Link |
|---|---|---|---|
| BEACON CRC | Other Identifier | Alias Study Number | |
| 2015-005805-35 | EudraCT Number | ||
| C4221009 | Other Identifier | Pfizer |
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
| Pierre Fabre Medicament | INDUSTRY |
| Ono Pharmaceutical Co., Ltd. | INDUSTRY |
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This is a multicenter, randomized, open-label, 3-arm Phase 3 study to evaluate encorafenib + cetuximab plus or minus binimetinib versus Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab, as controls, in patients with BRAFV600E mCRC whose disease has progressed after 1 or 2 prior regimens in the metastatic setting. The study contains a Safety Lead-in Phase in which the safety and tolerability of encorafenib + binimetinib + cetuximab will be assessed prior to the Phase 3 portion of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Safety Lead-in, Triplet Arm | Experimental | Encorafenib + binimetinib + cetuximab. |
|
| Doublet Arm | Experimental | Encorafenib + cetuximab. |
|
| Control Arm | Active Comparator | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Encorafenib | Drug | Orally, once daily. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| (Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs) | Cycle 1 (up to 28 days) | |
| (Safety Lead-in) Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting AEs were reported in this outcome measure. | Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
| (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. | Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
| (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants according to incidence of dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. | From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
| (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis | OS was defined as the time from randomization to death due to any cause. |
| Measure | Description | Time Frame |
|---|---|---|
| (Safety Lead-in) Objective Response Rate (ORR) by Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
| Measure | Description | Time Frame |
|---|---|---|
| (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Final Analysis | OS was defined as the time from randomization to death due to any cause. | From randomization to death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic Hospital | Phoenix | Arizona | 85054 | United States | ||
| Mayo Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39313594 | Derived | Kopetz S, Murphy DA, Pu J, Ciardiello F, Desai J, Van Cutsem E, Wasan HS, Yoshino T, Saffari H, Zhang X, Hamilton P, Xie T, Yaeger R, Tabernero J. Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. Nat Med. 2024 Nov;30(11):3261-3271. doi: 10.1038/s41591-024-03235-9. Epub 2024 Sep 23. | |
| 36653241 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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Participants were at least 18 years of age with confirmed metastatic colorectal cancer (CRC) whose disease had progressed after 1 or 2 prior regimens in the metastatic setting and whose tumor tissue was BRAF V600E-mutant as previously determined by a local assay at any time prior to Screening.
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| ID | Title | Description |
|---|---|---|
| FG000 | Combined Safety Lead-in | Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care. |
| FG001 | Phase 3: Triplet Arm |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 11, 2019 | May 1, 2020 |
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| Binimetinib |
| Drug |
Orally, twice daily. |
|
| Cetuximab | Drug | Standard of care. |
|
| Irinotecan | Drug | Standard of care. |
|
| Folinic Acid | Drug | Standard of care. |
|
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| 5-Fluorouracil | Drug | Standard of care. |
|
|
| From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm) |
| (Phase 3) Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR), where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Objective Response Rate (ORR) by BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Duration of Response (DOR) by Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Duration of Response (DOR) by BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Time to Response by Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Time to Response by BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Progression-Free Survival (PFS) by Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
| (Safety Lead-in) Progression-Free Survival (PFS) by BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
| (Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm | OS was defined as the time from randomization to death due to any cause. | From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm) |
| (Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm | OS was defined as the time from randomization to death due to any cause. | From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 89.1 weeks for triplet arm) |
| (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
| (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
| (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
| (Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The EORTC QLQ-C30 questionnaire consisted of 30 questions generating 5 functional scores (physical, role, cognitive, emotional, & social); a global health (GH) status/global quality of life scale score; 3 symptom scale scores (fatigue, pain, & nausea & vomiting); & 6 standalone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, & diarrhea) & perceived financial burden. All items were graded by severity experienced during previous week & used 4-point-scale (1: not at all, 2: a little, 3: quite a bit, 4: very much). The scores were converted to health-related quality of life (HRQoL) scale ranging from 0-100. Higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity). | Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
| (Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | FACT-C= Functional Assessment of Chronic Illness Therapy (FACIT), which assessed HRQoL of cancer participants & participants with other chronic illnesses. It consists of total 36 items (27 items of general version of FACT-C and disease-specific subscale containing 9 CRC-specific items), summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range:0-28, emotional well-being (6 items) range: 0-24, colorectal cancer subscale (9 items) range: 0-36; higher subscale score= better QoL. All single-item measures range: 0= 'Not at all' to 4= 'Very much'. Table summarizes functional well-being subscale, individual questions are linearly scaled & combined to form functional well-being subscale score (range 0-28). High score represents better QoL. | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
| (Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the participant and ranges from 0 to 100 (higher is better quality health). | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
| (Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The PGIC is a measure of participant's perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other participant reported outcome (PROs). For this assessment, participants answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse." | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032) | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032) | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032) | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
| (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
| (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
| (Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
| Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to more than or equal to (>=) Grade 3 based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities | Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: low/high systolic blood pressure (SBP): <= 90 millimeters of mercury (mmHg) with decrease from baseline of >= 20mmHg or >= 160mmHg with increase from baseline of >= 20mmHg, low or high diastolic blood pressure (DBP): <= 50mmHg with decrease from baseline of >= 15mmHg or >= 100mmHg with increase from baseline of >= 15mmHg, low or high pulse: <= 50 beats/min with decrease from baseline of >= 15 beats/min or >= 120 beats/min with increase from baseline of >= 15 beats/min, low or high temperature: <= 36 degree Celsius (deg C) or >= 37.5 deg C. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values | Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: heart rate- decrease from baseline > 25% and to a value < 50 and increase from baseline > 25% and to a value > 100. QT interval- new > 450 (millisecond) msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. QTcF- new > 450 msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score | Visual acuity was measured using the Snellen visual acuity conversion chart. This was determined by establishing the smallest optotypes that could be identified correctly by the participant at a given observation distance. Snellen visual acuity was reported as a Snellen fraction (m/M) in which the numerator (m) indicated the test distance and the denominator (M) indicated the distance at which the gap of the equivalent Landolt ring subtends 1 minute of arc. The LogMAR score was calculated as - log(m/M). The maximum increase in score of <= 0, 0 to < 0.1, 0.1 to < 0.2, 0.2 to < 0.3 and >=0.3 relative to baseline in LogMAR were reported in this endpoint. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment | Left ventricular ejection fraction (LVEF) abnormalities were defined according to CTCAE version 4.03 where Grade 0: Non-missing value below Grade 2, Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and < -20%, Grade 3: LVEF between 20% and 39% or absolute change from baseline <= -20%, Grade 4: LVEF lower than 20%. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported. | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
| Phoenix |
| Arizona |
| 85054 |
| United States |
| Mayo Clinic | Scottsdale | Arizona | 85259 | United States |
| City of Hope (City of Hope National Medical Center, City of Hope Medical Center) | Duarte | California | 91010 | United States |
| Compassionate Care Research Group, Inc. at Compassionate Cancer Care Medical Group, Inc. | Fountain Valley | California | 92708 | United States |
| Keck Hospital of USC - Norris Healthcare Center (HC3) | Los Angeles | California | 90033 | United States |
| Keck Hospital of USC | Los Angeles | California | 90033 | United States |
| LAC+USC Medical Center | Los Angeles | California | 90033 | United States |
| Norris Healthcare Center 3 (HC3) | Los Angeles | California | 90033 | United States |
| USC Eye Institute | Los Angeles | California | 90033 | United States |
| USC/Norris Comprehensive Cancer Center | Los Angeles | California | 90033 | United States |
| Hoag Memorial Hospital Presbyterian | Newport Beach | California | 92663 | United States |
| Harvard Eye Associates | Orange | California | 92868 | United States |
| Rocky Mountain Lions Eye Institute | Aurora | Colorado | 80045 | United States |
| University of Colorado Cancer Center - Anschutz Cancer Pavilion | Aurora | Colorado | 80045 | United States |
| University of Colorado Denver CTO (CTRC) | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) | Aurora | Colorado | 80045 | United States |
| University of Colorado Hospital Inpatient Pavillion' | Aurora | Colorado | 80045 | United States |
| Smilow Cancer Hospital at Yale - New Haven | New Haven | Connecticut | 06510 | United States |
| Temple Medical Center | New Haven | Connecticut | 06510 | United States |
| Yale University, Yale Cancer Center | New Haven | Connecticut | 06520 | United States |
| Smilow Cancer Hospital Care Center at North Haven | North Haven | Connecticut | 06473 | United States |
| The Lennar Foundation Medical Center | Coral Gables | Florida | 33146 | United States |
| Broward Health Medical Center | Fort Lauderdale | Florida | 33316 | United States |
| Dr. Clayton Berger (opthalmology) | Fort Lauderdale | Florida | 33316 | United States |
| Mehmet F. Hepgur, MD - Broward Health Medical Center | Fort Lauderdale | Florida | 33316 | United States |
| Mayo Clinic Florida | Jacksonville | Florida | 32224 | United States |
| Sylvester Comprehensive Cancer Center/UMHC | Miami | Florida | 33136 | United States |
| Sylvester at Kendall | Miami | Florida | 33176 | United States |
| Illinois CancerCare- Bloomington | Bloomington | Illinois | 61704 | United States |
| University of Chicago Medical Center | Chicago | Illinois | 60637 | United States |
| Illinois CancerCare- Galesburg | Galesburg | Illinois | 61401 | United States |
| University of Chicago Comprehensive Cancer Center at Silver Cross Hospital | New Lenox | Illinois | 60451 | United States |
| The University of Chicago Medicine Center for Advanced Care Orland Park | Orland Park | Illinois | 60462 | United States |
| Illinois CancerCare- Ottawa | Ottawa | Illinois | 61350 | United States |
| Illinois Cancer Care, PC | Peoria | Illinois | 61615 | United States |
| Illinois Eye Center | Peoria | Illinois | 61615 | United States |
| Carle Cancer Center | Urbana | Illinois | 61801 | United States |
| Indiana University Health Hospital | Indianapolis | Indiana | 46202 | United States |
| Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Investigational Drug Services IUHSCC | Indianapolis | Indiana | 46202 | United States |
| Sidney &Lois Eskenazi Hospital | Indianapolis | Indiana | 46202 | United States |
| IU Health Springmill | Indianapolis | Indiana | 46290 | United States |
| Baptist Health Floyd Cancer Center | New Albany | Indiana | 47150 | United States |
| University of Iowa Hospitals and Clinics | Iowa City | Iowa | 52242 | United States |
| The University of Kansas Clinical Research Center | Fairway | Kansas | 66205 | United States |
| The University of Kansas Hospital | Kansas City | Kansas | 66160 | United States |
| KU Eye | Prairie Village | Kansas | 66208 | United States |
| The University of Kansas Cancer Center and Medical Pavilion | Westwood | Kansas | 66205 | United States |
| The University of Kansas Cancer Center, Investigational Drug Services | Westwood | Kansas | 66205 | United States |
| Ochsner Clinic Foundation | New Orleans | Louisiana | 70121 | United States |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| The Investigational Drug Pharmacy (IDS) in the Sidney Kimmel Cancer Center at Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore | Maryland | 21287 | United States |
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
| Ophthalmic Consultants of Boston Inc | Boston | Massachusetts | 02114 | United States |
| Brigham & Women's Hospital | Boston | Massachusetts | 02115 | United States |
| Dana-Farber Cancer Institute (DFCI) | Boston | Massachusetts | 02215 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Siteman Cancer Center - St Peters | City of Saint Peters | Missouri | 63376 | United States |
| Siteman Cancer Center - West County | Creve Coeur | Missouri | 63141 | United States |
| SSM Health Saint Louis University Hospital | St Louis | Missouri | 63104 | United States |
| Barnes Jewish Hospital | St Louis | Missouri | 63110 | United States |
| Saint Louis University | St Louis | Missouri | 63110 | United States |
| SSM Health Saint Louis University Hospital | St Louis | Missouri | 63110 | United States |
| Washington University Infusion Center Pharmacy | St Louis | Missouri | 63110 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Siteman Cancer Center - South County | St Louis | Missouri | 63129 | United States |
| Memorial Sloan Kettering: Basking Ridge | Basking Ridge | New Jersey | 07920 | United States |
| Memorial Sloan Kettering: Commack | Commack | New York | 11725 | United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10065 | United States |
| Memorial Sloan Kettering: Rockefeller Outpatient Pavilion | New York | New York | 10065 | United States |
| Gabrail Cancer Center Research | Canton | Ohio | 44718 | United States |
| Cleveland Clinic Taussig Cancer Institute | Cleveland | Ohio | 44195 | United States |
| Casey Eye Institute-South Waterfront | Portland | Oregon | 97239 | United States |
| OHSU Center for Health and Healing | Portland | Oregon | 97239 | United States |
| OHSU Research Pharmacy Services | Portland | Oregon | 97239 | United States |
| Oregon Health and Science University | Portland | Oregon | 97239 | United States |
| Henry-Joyce Cancer Clinic | Nashville | Tennessee | 37232 | United States |
| Vanderbilt Eye Institute | Nashville | Tennessee | 37232 | United States |
| The University of Texas MD Anderson Cancer Center | Houston | Texas | 77030-4009 | United States |
| Scott & White Clinic - Temple Pavilion | Temple | Texas | 76504 | United States |
| Scott & White Medical Center - Temple | Temple | Texas | 76508 | United States |
| Spokane Eye Clinic | Spokane | Washington | 99204 | United States |
| Inland Imaging, LLC Holy Family Hospital | Spokane | Washington | 99208 | United States |
| Medical Oncology Associates, PS DBA Summit Cancer Centers | Spokane | Washington | 99208 | United States |
| Providence Holy Family Nuclear Medicine | Spokane | Washington | 99208 | United States |
| Medical Oncology Associates, PS DBA Summit Cancer Centers | Spokane Valley | Washington | 99216 | United States |
| University of Wisconsin Clinical Science Center | Madison | Wisconsin | 53792 | United States |
| CLINICA PERGAMINO S.A. (Centro de Investigacion Pergamino S.A.) | Pergamino | Buenos Aires | 2700 | Argentina |
| Centro Medico INFINITO | Santa Rosa | La Pampa Province | L6300EAN | Argentina |
| Centro Medico CAIPO (Centro para la Atención del paciente Oncológico) | San Miguel de Tucumán | Tucumán Province | T4000GTB | Argentina |
| Clinica Universitaria Reina Fabiola | Córdoba | X5004FHP | Argentina |
| Centro Oncologico Riojano Integral - CORI | La Rioja | 5300 | Argentina |
| St Vincent's Clinic | Darlinghurst | NEW South Wales (nsw) | 2010 | Australia |
| St Vincent's Hospital Sydney | Darlinghurst | NEW South Wales (nsw) | 2010 | Australia |
| Marsden Eye Specialists | Parramatta | NEW South Wales (nsw) | 2150 | Australia |
| Newcastle Eye Centre | Sydney | NEW South Wales (nsw) | 2300 | Australia |
| Mater Misericordiae Limited | South Brisbane | Queensland | 4101 | Australia |
| Central Adelaide Local Health Network Inc. operating as Royal Adelaide Hospital | Adelaide | South Australia | 5000 | Australia |
| Flinders Medical Centre | Bedford Park | South Australia | 5042 | Australia |
| Central Adelaide Local Health Network Inc. operating as The Queen Elizabeth Hospital | Woodville South | South Australia | 5011 | Australia |
| Monash Health Translation Precinct - Monash Health | Clayton | Victoria | 3168 | Australia |
| Austin Health | Heidelberg | Victoria | 3084 | Australia |
| Peter MacCallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| Klinikum Wels - Grieskirchen GmbH, Abteilung fuer Innere Medizin IV | Wels | Upper Austria | 4600 | Austria |
| Klinikum Wels-Grieskirchen GmbH, Abteilung fuer Augenheilkunde und Optometrie | Wels | Upper Austria | 4600 | Austria |
| Klinikum Wels-Grieskirchen GmbH, Abteilung fuer Innere Medizin II | Wels | Upper Austria | 4600 | Austria |
| Klinikum Wels-Grieskirchen GmbH, Institut fuer Nuklearmedizin | Wels | Upper Austria | 4600 | Austria |
| Klinikum Wels-Grieskirchen GmbH, Institut fuer Radiologie I | Wels | Upper Austria | 4600 | Austria |
| DZU, Diagnose Zentrum Urania GmbH | Vienna | 1010 | Austria |
| AKH Wien | Vienna | 1090 | Austria |
| Medizinische Universitaet Wien/AKH Wien | Vienna | 1090 | Austria |
| Medizinische Universität Wien/AKH Wien | Vienna | 1090 | Austria |
| Centre Hospitalier de l'Ardenne - Site de Libramont | Libramont-Chevigny | Luxembourg | 6800 | Belgium |
| AZ Sint-Jan Brugge - Oostende AV - Campus Sint-Jan - Oncology | Bruges | WEST Vlaanderen | 8000 | Belgium |
| Imelda Ziekenhuis | Bonheiden | 2820 | Belgium |
| Grand Hopital de Charleroi (GHdC) | Charleroi | 6000 | Belgium |
| UZ Antwerpen | Edegem | 2650 | Belgium |
| AZ Maria Middelares | Ghent | 9000 | Belgium |
| University Hospital Gasthuisberg (UZ Leuven) | Leuven | 3000 | Belgium |
| Centre Hospitalier Universitaire (CHU) de Liege | Liège | 4000 | Belgium |
| CHC Saint Joseph | Liège | 4000 | Belgium |
| AZ Delta Roeselaere-Menen | Roeselaere | 8800 | Belgium |
| Centre Hospitalier Regional (CHR) - Verviers | Verviers | 4800 | Belgium |
| CEMES Centro Medico Especializado em Oftalmologia | Cachoeiro de Itapemirim | Espírito Santo | 29300-045 | Brazil |
| Centro de Pesquisas Clínicas em Oncologia | Cachoeiro de Itapemirim | Espírito Santo | 29308-014 | Brazil |
| Hospital Evangelico de Cachoeiro de Itapemirim | Cachoeiro de Itapemirim | Espírito Santo | 29308-055 | Brazil |
| Hospital do Olho | Salvador | Estado de Bahia | 41820-020 | Brazil |
| CENOB - Centro de Oncologia da Bahia SS Ltda / Oncovida | Salvador | Estado de Bahia | 41820-021 | Brazil |
| Instituto Vizibelli | Belo Horizonte | Minas Gerais | 30110-921 | Brazil |
| CENANTRON - Centro Avancado de Tratamento Oncologic | Belo Horizonte | Minas Gerais | 30130-090 | Brazil |
| Fundação Universidade de Caxias do Sul | Caxias do Sul | Rio Grande do Sul | 95070-560 | Brazil |
| Daniel Lubisco Pandolfi | Lajeado | Rio Grande do Sul | 95900-000 | Brazil |
| Sociedade Beneficencia e Cardade de Lajeado/Hospital Bruno Born | Lajeado | Rio Grande do Sul | 95900-000 | Brazil |
| Sociedade Beneficencia e Cardade de Lajeado/Hospital Bruno Born | Lajeado | Rio Grande do Sul | 95900-010 | Brazil |
| Associacao Hospitalar Beneficente Sao Vicente de Paulo / Hospital Sao Vicente de Paulo | Passo Fundo | Rio Grande do Sul | 99010-080 | Brazil |
| Consultorio Medico de Oftalmologia - Dr. Ricardo Tres | Passo Fundo | Rio Grande do Sul | 99010-080 | Brazil |
| Hospital Sao Vicente de Paulo | Passo Fundo | Rio Grande do Sul | 99010-090 | Brazil |
| Thiago Vernetti Ferreira | Pelotas | Rio Grande do Sul | 96010-140 | Brazil |
| Leandro Becker | Pelotas | Rio Grande do Sul | 96015-280 | Brazil |
| Fernanda Mendes | Pelotas | Rio Grande do Sul | 96020-080 | Brazil |
| UPCO - Unidade de Pesquisas Clinicas em Oncologia | Pelotas | Rio Grande do Sul | 96020-080 | Brazil |
| Fernanda Lauermann | Pelotas | Rio Grande do Sul | 96020-260 | Brazil |
| Diogo Duarte Torre | Porto Alegre | Rio Grande do Sul | 90020-013 | Brazil |
| Farmacia Central da Irmandade da Santa Casa de Misericordia de Porto Alegre | Porto Alegre | Rio Grande do Sul | 90020-090 | Brazil |
| Irmandade da Santa Casa de Misericordia de Porto Alegre | Porto Alegre | Rio Grande do Sul | 90020-090 | Brazil |
| Nucleo de Novos Tratamentos em Cancer | Porto Alegre | Rio Grande do Sul | 90050-170 | Brazil |
| Centro de Pesquisa Clínica de Oncologia e Hematologia - Hospital Mãe de Deus/AESC | Porto Alegre | Rio Grande do Sul | 90110-270 | Brazil |
| Clinica de Oftalmologia Lavinsky | Porto Alegre | Rio Grande do Sul | 90470-340 | Brazil |
| Hospital Mãe de Deus | Porto Alegre | Rio Grande do Sul | 90880-480 | Brazil |
| Giuliano Santos Borges - ME / Clinica de Neoplasias Litoral - Centro de Novos Tratamentos Itajai | Itajaí | Santa Catarina | 88301-220 | Brazil |
| Clinica Toller | Barretos | São Paulo | 14780-110 | Brazil |
| Olhos Centro Diagnostico e Laser LTDA | Barretos | São Paulo | 14780-300 | Brazil |
| Fundacao Pio XII | Barretos | São Paulo | 14784-400 | Brazil |
| FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC | Santo André | São Paulo | 09060-650 | Brazil |
| FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC | Santo André | São Paulo | 09060-870 | Brazil |
| Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto | São José do Rio Preto | São Paulo | 15090-000 | Brazil |
| CEPOS - Centro de Estudos e Pesquisas Oncologicas de Sorocaba | Sorocaba | São Paulo | 18030-075 | Brazil |
| Instituto de Oncologia de Sorocaba "Dr. Gilson Delgado" | Sorocaba | São Paulo | 18030-200 | Brazil |
| Karen Miyuki Kubokawa Shorer | Sorocaba | São Paulo | 18040-425 | Brazil |
| Oftalmologia Diagnostica de Sorocaba (ODS) | Sorocaba | São Paulo | 18047-620 | Brazil |
| Instituto de Ensino e Pesquisa São Lucas | São Paulo | 01236-030 | Brazil |
| Instituto de Ensino e Pesquisa São Lucas - Pharmacy | São Paulo | 01242-020 | Brazil |
| Hospital Leforte | São Paulo | 01507-000 | Brazil |
| IPEPO - Instituto da Visao | São Paulo | 04038-020 | Brazil |
| Eye Care Centre, Vancouver General Hospital | Vancouver | British Columbia | V5Z 3N9 | Canada |
| BC Cancer, Vancouver Center | Vancouver | British Columbia | V5Z 4E6 | Canada |
| The Ottawa Hospital Cancer Centre | Ottawa | Ontario | K1H 8L6 | Canada |
| Sunnybrook Research Institute | Toronto | Ontario | M4N 3M5 | Canada |
| Mount Sinai Hospital | Toronto | Ontario | M5G 1X5 | Canada |
| Centre integre universitaire de sante et de services sociaux de l'Ouest-de-l'Ile-de-Montreal | Montreal | Quebec | H3T 1M5 | Canada |
| Instituto Clinico Oncologico del Sur (ICOS) | Temuco | Araucania | 4810469 | Chile |
| Hospital Clinico Vina Del Mar | Viña del Mar | V Region Valparaiso | 2520612 | Chile |
| Ocni ordinace Oftalpro s.r.o. | Brno | 603 00 | Czechia |
| Masarykuv onkologicky ustav | Brno | 656 53 | Czechia |
| Fakultni nemocnice Hradec Kralove | Hradec Králové | 500 05 | Czechia |
| Fingerlanduv ustav patologie | Hradec Králové | 500 05 | Czechia |
| I. interni kardioangiologicka klinika | Hradec Králové | 500 05 | Czechia |
| Klinika nemoci koznich a pohlavnich | Hradec Králové | 500 05 | Czechia |
| Nemocnicni lekarna - Usek klinickych studii | Hradec Králové | 500 05 | Czechia |
| Ocni klinika | Hradec Králové | 500 05 | Czechia |
| Radiologicka klinika | Hradec Králové | 500 05 | Czechia |
| Fakultni nemocnice Olomouc, I. interni klinika - kardiologicka | Olomouc | 779 00 | Czechia |
| Fakultni nemocnice Olomouc, Lekarna | Olomouc | 779 00 | Czechia |
| Fakultni nemocnice Olomouc | Olomouc | 779 00 | Czechia |
| Odense University Hospital (OUH) | Odense C | DK-5000 | Denmark |
| Hopital Jean Minjoz | Besançon | 25030 | France |
| CHU Morvan | Brest | 29609 | France |
| Centre Ophtalmologique - Pole Vision - Clinique Val d'Ouest | Écully | 69130 | France |
| Centre Leon Berard | Lyon | 69373 | France |
| ICM Val d'Aurelle | Montpellier | 34298 | France |
| CHU HOTEL-Dieu | Nantes | 44093 | France |
| Hopital Georges Pompidou | Paris | 75015 | France |
| Centre hospitalier national d'ophtalmologie des Quinze-Vingts | Paris | 75571 | France |
| Centre Hospitalier National d'Opthalmologie des Quinze-Vingts (CHNO des XV-XX) | Paris | 75571 | France |
| CHU Robert Debre | Reims | 51092 | France |
| SCM Centre d'ophtalmologie | Saint Jeand de Vedas | 34430 | France |
| CHU Toulouse - Purpan, hopital Pierre-Paul Riquet | Toulouse | 31057 | France |
| CHU Toulouse-Institut Inuversitaire du Cancer Toulouse | Toulouse | 31059 | France |
| CHU Toulouse-Rangueil | Toulouse | 31059 | France |
| Gustave Roussy | Villejuif | 94805 | France |
| Universitaetsklinikum Tuebingen | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| Universitaetsklinikum Ulm | Ulm | Baden-Wurttemberg | 89081 | Germany |
| Augenklinik der Universitaet Muenchen | Munich | Bavaria | 80336 | Germany |
| LMU Klinikum der Universitaet Muenchen, Campus Grosshadern | Munich | Bavaria | 81377 | Germany |
| Augenarzt-Gemeinschaftspraxis Dr.med.Andreas Kind & Dr.med. Ute Kariger-Schweigert | Falkensee | Brandenburg | 14612 | Germany |
| Medizinische Hochschule Hannover (MHH) | Hanover | Lower Saxony | 30625 | Germany |
| Medizinische Hochschule Hannover | Hanover | Lower Saxony | 30625 | Germany |
| Institut f. Pathologie - Ruhr-Universitaet Bochum, Prof. Dr. med. Andrea Tannapfel | Bochum | North Rhine Westfalia | 44789 | Germany |
| Kliniken Essen Mitte / Knappschaftskrankenhaus | Essen | North Rhine-Westphalia | 35136 | Germany |
| Praxis fuer Augenheilkunde Dr. Edmund Meyer-Schwickerath | Essen | North Rhine-Westphalia | 45131 | Germany |
| Kliniken Essen-Mitte | Essen | North Rhine-Westphalia | 45136 | Germany |
| Universitaetsklinikum Essen (AoeR), Innere Klinik (Tumorforschung), Westdeutsches Tumorzentrum | Essen | North Rhine-Westphalia | 45147 | Germany |
| Universitaetsklinikum Essen; Diagnostischeu. Interventionelle Radiologie u. Neuroradiologie | Essen | North Rhine-Westphalia | 45147 | Germany |
| Universitaetsklinikum Essen; Nuklearmedizin | Essen | North Rhine-Westphalia | 45147 | Germany |
| Universitaetsklinikum Essen; Zentralapotheke | Essen | North Rhine-Westphalia | 45147 | Germany |
| Evang. Krankenhaus Essen - Werden; Klinik fuer Augenheilkunde | Essen | North Rhine-Westphalia | 45239 | Germany |
| Kliniken Essen Mitte / Knappschaftskrankenhaus | Essen | North Rhine-Westphalia | 45276 | Germany |
| Augentagesklinik Maria-Hilf Krankenhaus | Mönchengladbach | North Rhine-Westphalia | 41063 | Germany |
| Kliniken Maria Hilf GmbH - Franziskuskrankenhaus | Mönchengladbach | North Rhine-Westphalia | 41063 | Germany |
| Kliniken Maria Hilf GmbH; Klinik fuer Radiologie | Mönchengladbach | North Rhine-Westphalia | 41063 | Germany |
| Lukaskrankenhaus Neuss; Zentrale Apotheke | Neuss | North Rhine-Westphalia | 41464 | Germany |
| Augenarzt Praxis Dr. med. Petra Huelsmann | Worms | Rhineland-Palatinate | 67547 | Germany |
| Gemeinschaftspraxis fuer Radiologie und Nuklearmedizin, Standort Worms | Worms | Rhineland-Palatinate | 67547 | Germany |
| Martin Apotheke | Worms | Rhineland-Palatinate | 67547 | Germany |
| Onkologische Schwerpunktpraxis Worms | Worms | Rhineland-Palatinate | 67547 | Germany |
| Praxisgemeinschaft Kruse + Hofstaetter | Worms | Rhineland-Palatinate | 67547 | Germany |
| Evangelisches Waldkrankenhaus Spandau | Berlin | 13589 | Germany |
| Universitaetsklinikum Carl Gustav Carus der Technischen Universitaet Dresden | Dresden | 01307 | Germany |
| Universitaetsklinikum Hamburg Eppendorf, Klinik fuer Augenheilkunde | Hamburg | 20246 | Germany |
| Facharztzentrum Eppendorf | Hamburg | 20249 | Germany |
| Universitaetsklinikum Hamburg Eppendorf, Zentrum fuer Radiologie und Endoskopie | Hamburg | 20251 | Germany |
| ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld | Hamburg | 22045 | Germany |
| HKS Kardiologische Praxis am Israelitischen Krankenhaus | Hamburg | 22297 | Germany |
| Radiologie im Israelitischen Krankenhaus | Hamburg | 22297 | Germany |
| Zala Megyei Szent Rafael Korhaz - Onkologiai Osztaly | Zalaegerszeg | Zala County | H-8900 | Hungary |
| Szent Margit Kórház | Budapest | 1032 | Hungary |
| Eszak-Pesti Centrumkorhaz-Honvedkorhaz | Budapest | 1062 | Hungary |
| Magyar Honvedseg Egeszsegugyi Kozpont | Budapest | 1062 | Hungary |
| Egyesitett Szent Istvan es Szent Laszlo Korhaz-Rendelointezet | Budapest | 1097 | Hungary |
| Uzsoki Utcai Korhaz | Budapest | 1145 | Hungary |
| Debreceni Egyetem Klinikai Kozpont | Debrecen | 4032 | Hungary |
| Pecsi Tudomanyegyetem Altalanos Orvostudomanyi Kar | Pécs | 7624 | Hungary |
| Pecsi Tudomanyegyetem Klinikai Kozpont | Pécs | 7624 | Hungary |
| Tel Aviv Sourasky Medical Center - Oncology | Tel Aviv | NAP | 6423906 | Israel |
| The Barzilai Medical Center - Oncology Institute | Ashkelon | 7830604 | Israel |
| Soroka University Medical Center | Beersheba | 8410101 | Israel |
| MOR Institute | Bnei Brak | 5126413 | Israel |
| Ein-Karem Department of Medical Imaging of Hadassah Medical Organization, Hadassah Medical Center, | Jerusalem | 9112001 | Israel |
| Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem | Jerusalem | 9112001 | Israel |
| Pharmacy of Hadassah Medical Organization, Hadassah Medical Center, Ein-Karem | Jerusalem | 9112001 | Israel |
| Mt. Scopus Department of Medical Imaging of Hadassah Medical Organization, | Jerusalem | 91240 | Israel |
| Imaging Department of Meir Medical Center | Kfar Saba | 4428164 | Israel |
| Meir Medical Center | Kfar Saba | 4428164 | Israel |
| Pharmacy of Rabin Medical Center, Beilinson Hospital | Petah Tikva | 4941492 | Israel |
| Rabin Medical Center, Beilinson Hospital | Petah Tikva | 4941492 | Israel |
| The Chaim Sheba Medical Center | Tel Litwinsky | 5262100 | Israel |
| Ospedali Riuniti Umberto I | Torrette Di Ancona | Ancona | 60020 | Italy |
| ASST Bergamo Ovest, Ospedale Treviglio Caravaggio di Trevigl | Treviglio | Bergamo | 24047 | Italy |
| Oculistica, ASST Papa Giovanni XXIII | Bergamo | BG | 24127 | Italy |
| Oncologia, ASST Papa Giovanni XXIII | Bergamo | BG | 24127 | Italy |
| Clinica di Oncologia Medica AOU di Cagliari Presidio Duilio Casula Monserrato | Monserrato | Cagliari | 09042 | Italy |
| Farmacia AOU di Cagliari Presidio Duilio Casula Monserrato | Monserrato | Cagliari | 09042 | Italy |
| Radiologia AOU di Cagliari Presidio Duilio Casula Monserrato | Monserrato | Cagliari | 09042 | Italy |
| Oculistica - ASST Cremona, Ospedale di Cremona | Cremona | CR | 26100 | Italy |
| SC Farmacia Aziendale - ASST Cremona, Ospedale di Cremona | Cremona | CR | 26100 | Italy |
| SC Oncologia - ASST Cremona, Ospedale di Cremona | Cremona | CR | 26100 | Italy |
| U.O. Oculistica, Istituto Clinico HUMANITAS | Rozzano | Milano | 20089 | Italy |
| U.O. di Oncologia ed Ematologia, Istituto Clinico HUMANITAS | Rozzano (MI) | Milan | 20089 | Italy |
| IRCCS Ospedale San Raffaele - U.O. di Medicina Oncologica | Milan | MI | 20132 | Italy |
| Servizio di Farmacia - IRCCS Ospedale San Raffaele | Milan | MI | 20132 | Italy |
| S.C. Radiologia diagnostica e interventistica - Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | MI | 20133 | Italy |
| SC Oncologia Medica 1, SS Oncologia Medica Gastroenterologica | Milan | MI | 20133 | Italy |
| Cardiologia per i pazienti oncologici - Istituto Oncologico Veneto I.R.C.C.S | Padova | PD | 35128 | Italy |
| Clinica Oculistica - Azienda Ospedaliera di Padova | Padova | PD | 35128 | Italy |
| U.O. Oncologia Medica 1 - Istituto Oncologico Veneto I.R.C.C.S | Padova | PD | 35128 | Italy |
| Policlinico S.Orsola Malpighi, AOU di Bologna - Oncologia Medica | Bologna | 40138 | Italy |
| Divisione Anatomia Patologica Presidio San Giovanni di Dio | Cagliari | 09124 | Italy |
| Oculistica AOU di Cagliari Presidio San Giovanni di Dio | Cagliari | 09124 | Italy |
| Dipartimento Neuromuscoloscheletrico e Organi di Senso, "Oncologia Oculare Unit" | Florence | 50134 | Italy |
| SC oncologia Medica I - Azienda Ospedaliero Universitaria Careggi | Florence | 50134 | Italy |
| Radiologia | Milan | 20141 | Italy |
| Unita di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini | Milan | 20141 | Italy |
| Grande Ospedale Metropolitano Niguarda | Milan | 20162 | Italy |
| Dipartimento Interaziendale Farmaceutico - AOU Policlinico di Modena | Modena | 41124 | Italy |
| SC di Oftalmologia - AOU Policlinico di Modena | Modena | 41124 | Italy |
| SC di Radiologia, Dipartimento Interaziendale integrato Diagnostica per Immagini | Modena | 41124 | Italy |
| SSD Day Hospital Oncologico - Dipartimento ad attivita integrata di Oncologia, Ematologia | Modena | 41124 | Italy |
| AOU Universita degli Studi della Campania L. Vanvitelli - DAI di Medicina Interna e Specialistica | Naples | 80131 | Italy |
| AOU Universita degli Studi della Campania L. Vanvitelli - U. Ma.Ca. | Naples | 80131 | Italy |
| AOU Universita degli Studi della Campania L. Vanvitelli | Naples | 80131 | Italy |
| AOU Universita degli Studi della Campania L. Vanvitelli | Naples | 80138 | Italy |
| UO Oculistica - AOU Pisana, Stabilimento Ospedaliero di Cisanello | Pisa | 56124 | Italy |
| SOD Radiodiagnostica 3 - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara | Pisa | 56126 | Italy |
| UO Farmaceutica, Gestione del Farmaco - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara | Pisa | 56126 | Italy |
| UO Oncologia Medica 2 - AOU Pisana, Stabilimento Ospedaliero di Santa Chiara | Pisa | 56126 | Italy |
| U.O.S.D. Oncologia Medica, Dipartimento di Medicina - Fondazione PTV Policlinico Tor Vergata | Roma | 00133 | Italy |
| U.O.S.D. Patologie Retiniche - Fondazione PTV Policlinico Tor Vergata | Roma | 00133 | Italy |
| Chayagasaka Eye Clinic | Nagoya | Aichi-ken | 464-0092 | Japan |
| Aichi Cancer Center Hospital | Nagoya | Aichi-ken | 464-8681 | Japan |
| National Cancer Center Hospital East | Kashiwa-shi | Chiba | 277-8577 | Japan |
| Hokkaido University Hospital | Sapporo | Hokkaido | 060-8648 | Japan |
| Kanazawa University Hospital | Kanazawa | Ishikawa-ken | 920-8641 | Japan |
| St. Marianna University School of Medicine Hospital | Kawasaki | Kanagawa | 216-8511 | Japan |
| Tsukahara Eye Clinic | Yokohama | Kanagawa | 241-0821 | Japan |
| Kanagawa Cancer Center | Yokohama | Kanagawa | 241-8515 | Japan |
| Osaka University Hospital Laboratory for Clinical Investigation | Suita | Osaka | 565-0871 | Japan |
| National Cancer Center Hospital | Chuo-ku | Tokyo | 104-0045 | Japan |
| National Hospital Organization Kyushu Cancer Center | Fukuoka | 811-1395 | Japan |
| Kyushu Central Hospital of the Mutual Aid Association of Public School Teachers | Fukuoka | 815-8588 | Japan |
| National Hospital Organization Osaka National Hospital | Osaka | 540-0006 | Japan |
| Consultorio dentro de la Torre Medica Dalinde (Oncologia Medica) | Mexico City | Cuauhtemoc | 06760 | Mexico |
| Superare Centro de Infusion S.A. de C.V. | Delegacion Cuauhtemoc | Mexico City | 06760 | Mexico |
| Rijnstate Hospital Arnhem | Arnhem | Gelderland | 6815 AD | Netherlands |
| Rijnstate Hospital Velp | Velp | Gelderland | 6883 AZ | Netherlands |
| Maastricht University Medical Center (MUMC) | Maastricht | Limburg | 6229HX | Netherlands |
| The Netherlands Cancer Institute | Amsterdam | North Holland | 1066 CX | Netherlands |
| Onze Lieve Vrouwen Gasthuis | Amsterdam | North Holland | 1091 AC | Netherlands |
| Haga Ziekenhuis | The Hague | South Holland | 2545 AA | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584 CX | Netherlands |
| Universitair Medisch Centrum Utrecht | Utrecht | 3584CX | Netherlands |
| Colosseum Øyelegesenter C/O LB Holdings AS | Lommedalen | 1350 | Norway |
| Colosseum Øyelegesenter C/O LB Holdings AS | Oslo | 0369 | Norway |
| Oslo universitetssykehus, Radiumhospitalet | Oslo | 0379 | Norway |
| Sykehusapoteket Oslo, Radiumhospitalet | Oslo | 0379 | Norway |
| Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza | Brzozów | 36-200 | Poland |
| Wojewodzki Szpital Zespolony, Oddzial Onkologiczny | Elblag | 82-300 | Poland |
| Szpital Specjalistyczny im. L. Rydygiera w Krakowie Sp.z.o.o. | Krakow | 31-826 | Poland |
| Europejskie Centrum Zdrowia Otwock, Szpital im. F. Chopina | Otwock | 05-400 | Poland |
| NZOZ Centrum Medyczne HCP | Poznan | 61-485 | Poland |
| NZOZ Przychodnia Specjalistyczna GUTMED | Poznan | 61495 | Poland |
| MAGODENT Sp. z o.o. Szpital Elblaska | Warsaw | 01-748 | Poland |
| Regional Budgetary Healthcare Institution Kursk Regional Clinical | Kursk | Kursk Oblast | 305524 | Russia |
| Evimed Llc | Chelyabinsk | 454048 | Russia |
| Federal State Budget Institution "N.N. Blokhin Russian Cancer Research Center" of the | Moscow | 115478 | Russia |
| Federal State Budget Institution "N.N. Blokhin Russian Cancer Research Center" | Moscow | 115478 | Russia |
| A. Tsyb Medical Radiological Research Center - branch of the | Obninsk | 249036 | Russia |
| State Budgetary Educational Institution of Higher Professional Education First Saint Petersburg | Saint Petersburg | 197022 | Russia |
| Seoul National University Bundang Hospital | Seongnam-si | Gyeonggi-do | 13620 | South Korea |
| Ajou University Hospital | Suwon | Gyeonggi-do | 16499 | South Korea |
| Hallym University Sacred Heart Hospital | Anyang | Gyeonggido | 14068 | South Korea |
| Chonnam National University Hwasun Hospital | Hwasun-gun | Jeollanam-do | 58128 | South Korea |
| Korea University Guro Hospital | Seoul | Seoul Teugbyeolsi | 08308 | South Korea |
| Dong-A University Hospital | Busan | 49201 | South Korea |
| Gachon University Gil Medical Center | Incheon | 21565 | South Korea |
| Korea University Anam Hospital IRB | Seoul | 02841 | South Korea |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Severance Hospital, Yonsei University Health System | Seoul | 03722 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Samsung Medical Center | Seoul | 06351 | South Korea |
| The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | 06591 | South Korea |
| Complejo Hospitalario de Jaen | Jaén | Andalusia | 23007 | Spain |
| Sercosa - Clinica de las Nieves | Jaén | Andalusia | 23007 | Spain |
| Hospital Universitario Son Espases | Palma de Mallorca | Balearic Islands | 07010 | Spain |
| Institut Catala d'Oncologia | L'Hospitalet de Llobregat | Barcelona | 08908 | Spain |
| Hospital Universitari Parc Tauli | Sabadell | Barcelona | 08208 | Spain |
| Hospital Universitario Reina Sofía | Córdoba | Cordona | 14004 | Spain |
| Hospital Nuestra Señora del Rosario | Madrid | Madrid, Communidad Delaware | 28006 | Spain |
| Hospital Universitari Sant Joan de Reus | Reus | Tarragona | 43204 | Spain |
| Hospital del Mar | Barcelona | 08003 | Spain |
| Clinica Corachan | Barcelona | 08017 | Spain |
| Hospital Quiron Salud Barcelona | Barcelona | 08023 | Spain |
| Cetir Centre Medic S.L. | Barcelona | 08029 | Spain |
| Hospital Universitario Vall d'Hebron | Barcelona | 08035 | Spain |
| Hospital Universitario de Burgos | Burgos | 09006 | Spain |
| Consulta Dr. Juan Carlos Castillo Dominguez | Córdoba | 14008 | Spain |
| Gabinete Radiologico Dr. Pita | Madrid | 28006 | Spain |
| Hospital General Universitario Gregorio Maranon | Madrid | 28007 | Spain |
| Hospital Universitario Ramón y Cajal | Madrid | 28034 | Spain |
| Hospital Clinico San Carlos | Madrid | 28040 | Spain |
| Hospital Universitario Fundacion Jimenez Diaz | Madrid | 28040 | Spain |
| Hospital Universitario 12 de Octubre | Madrid | 28041 | Spain |
| Hospital Universitario La Paz | Madrid | 28046 | Spain |
| Hospital HM Universitario Sanchinarro | Madrid | 28050 | Spain |
| Hospital Universitario Virgen del Rocio | Seville | 41013 | Spain |
| Clinica Oftalvist | Valencia | 46004 | Spain |
| Fundacion Instituto Valenciano de Oncologia | Valencia | 46009 | Spain |
| Hospital Clinico Universitario de Valencia | Valencia | 46010 | Spain |
| Hospital General Universitario de Valencia | Valencia | 46014 | Spain |
| Hospital Quiron Salud Zaragoza | Zaragoza | 50006 | Spain |
| Hospital Universitario Miguel Servet | Zaragoza | 50009 | Spain |
| Changhua Christian Hospital | Changhua | Changhua County | 500 | Taiwan |
| Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City | 807 | Taiwan |
| China Medical University Hospital | Taichung | 40447 | Taiwan |
| National Cheng Kung University Hospital | Tainan | 704 | Taiwan |
| National Taiwan University Hospital | Taipei | 10002 | Taiwan |
| Chang Gung Memorial Hospital, Linkou | Taoyuan City | 333 | Taiwan |
| Ege University Medical Faculty | Izmir | Bornova | 35040 | Turkey (Türkiye) |
| Izmir Medical Park Hospital - Medical Oncology | Izmir | Izmir, Karsiyaka | 35575 | Turkey (Türkiye) |
| Medeniyet University Goztepe Training and Research Hospital | Istanbul | Kadikoy | 34722 | Turkey (Türkiye) |
| Hacettepe University Medical Faculty | Ankara | 06230 | Turkey (Türkiye) |
| Uludag University Hospital | Bursa | 16059 | Turkey (Türkiye) |
| Trakya Universitesi Tip Fakultesi | Edirne | 22030 | Turkey (Türkiye) |
| Inonu Universitesi Turgut Ozal Medical Center | Malatya | 44280 | Turkey (Türkiye) |
| Oftalmolohycheskyi tsentr "Vzghliad" MTs | Dnipropetrovsk | Dnipropetrovsk Oblast | 41100 | Ukraine |
| Oftalmolohycheskyi tsentr "Vzghliad" MTs | Dnipropetrovsk | Dnipropetrovsk Oblast | 49027 | Ukraine |
| Derzhavnyi zaklad, Dnipropetrovska medychna akademiia Ministerstva okhorony zdorovia Ukrainy | Dnipropetrovsk | Dnipropetrovsk Oblast | 49102 | Ukraine |
| Komumalnyi zaklad, Dnipropetrovska miska bahatoprofilna klinichna likarnia Nº4 | Dnipropetrovsk | Dnipropetrovsk Oblast | 49102 | Ukraine |
| Kyivska klinichna likarnia na zaliznychnomu transporti No3 filii Tsentr okhorony zdorov'ia PAT | Kyiv | Kyivska Oblast' | 02096 | Ukraine |
| Natsionalnyi medychnyi universytet imeni O.O Bohomltsia, kafedra onkolohii | Kyiv | Kyivska Oblast' | 02096 | Ukraine |
| Natsionalnyi medychnyi universytet imeni O.O Bohomltsia, kafedra oftalmolohii | Kyiv | Kyivska Oblast | 01601 | Ukraine |
| Oleksandrivska klinichna likarnia mista Kyieva | Kyiv | Kyivska Oblast | 01601 | Ukraine |
| Kyivskyi miskyi klinichnyi onkotsentr | Kyiv | Kyivska Oblast | 03115 | Ukraine |
| Vinnytskyi oblasnyi klinichnyi onkolohichnyi dyspanser, viddilennia khimioterapii | Vinnytsia | Vinnytsia Oblast | 21029 | Ukraine |
| DVNZ "Uzhhorodskyi natsionalnyi universytet" | Uzhhorod | Zakarpattia Oblast | 88000 | Ukraine |
| TOV "Zakarpatskyi Tsentr Mikrokhirurhii Oka" | Uzhhorod | Zakarpattia Oblast | 88000 | Ukraine |
| Tsentralna miska klinichna likarnia, Miskyi onkolohichnyi tsentr | Uzhhorod | Zakarpattia Oblast | 88000 | Ukraine |
| NHS Grampian - Aberdeen Royal Infirmary | Aberdeen | Aberdeenshire Scotland | AB25 2ZN | United Kingdom |
| King Edward V11 Hospital | Windsor | Berkshire | SL4 3DP | United Kingdom |
| Beatson West of Scotland Cancer Centre | Glasglow | Glasglow City, Scotland | G12 0YH | United Kingdom |
| University Hospitals Birmingham NHS Foundation Trust Queen Elizabeth Hospital | Birmingham | WEST Midlands | B15 2TH | United Kingdom |
| Hammersmith Hospital, Imperial College Healthcare NHS Trust | London | W12 0HS | United Kingdom |
| Imperial College Healthcare NHS Trust, Hammersmith Hospital | London | W12 0HS | United Kingdom |
| Sarah Cannon Research Institute UK | London | W1G 6AD | United Kingdom |
| Imperial College Healthcare NHS Trust, Charing Cross Hospital | London | W6 8RF | United Kingdom |
| The Christie NHS Foundation Trust - Christie Hospital | Manchester | M20 4BX | United Kingdom |
| Taieb J, Lonardi S, Desai J, Folprecht G, Gallois C, Marques EP, Khan S, Castagne C, Wasan H. Adverse Events Associated with Encorafenib Plus Cetuximab in Patients with BRAFV600E-mutant Metastatic Colorectal Cancer: An in-depth Analysis of the BEACON CRC Study. Clin Colorectal Cancer. 2023 Mar;22(1):59-66. doi: 10.1016/j.clcc.2022.12.003. Epub 2022 Dec 24. |
| 35654691 | Derived | Stintzing S, Seufferlein T, Rose C, Reichenbach F, Luftner D. Encorafenib in Combination With Cetuximab After Systemic Therapy in Patients With BRAFV600E Mutant Metastatic Colorectal Cancer: German Health Technology Assessment-Driven Analyses From the BEACON CRC Study. Clin Colorectal Cancer. 2022 Sep;21(3):244-251. doi: 10.1016/j.clcc.2022.04.002. Epub 2022 May 5. |
| 35653981 | Derived | Kopetz S, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Belani A, Zhang X, Tabernero J. Quality of life with encorafenib plus cetuximab with or without binimetinib treatment in patients with BRAF V600E-mutant metastatic colorectal cancer: patient-reported outcomes from BEACON CRC. ESMO Open. 2022 Jun;7(3):100477. doi: 10.1016/j.esmoop.2022.100477. Epub 2022 May 30. |
| 33503393 | Derived | Tabernero J, Grothey A, Van Cutsem E, Yaeger R, Wasan H, Yoshino T, Desai J, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Elez E, Gollerkeri A, Maharry K, Christy-Bittel J, Kopetz S. Encorafenib Plus Cetuximab as a New Standard of Care for Previously Treated BRAF V600E-Mutant Metastatic Colorectal Cancer: Updated Survival Results and Subgroup Analyses from the BEACON Study. J Clin Oncol. 2021 Feb 1;39(4):273-284. doi: 10.1200/JCO.20.02088. |
| 31566309 | Derived | Kopetz S, Grothey A, Yaeger R, Van Cutsem E, Desai J, Yoshino T, Wasan H, Ciardiello F, Loupakis F, Hong YS, Steeghs N, Guren TK, Arkenau HT, Garcia-Alfonso P, Pfeiffer P, Orlov S, Lonardi S, Elez E, Kim TW, Schellens JHM, Guo C, Krishnan A, Dekervel J, Morris V, Calvo Ferrandiz A, Tarpgaard LS, Braun M, Gollerkeri A, Keir C, Maharry K, Pickard M, Christy-Bittel J, Anderson L, Sandor V, Tabernero J. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N Engl J Med. 2019 Oct 24;381(17):1632-1643. doi: 10.1056/NEJMoa1908075. Epub 2019 Sep 30. |
| 30892987 | Derived | Van Cutsem E, Huijberts S, Grothey A, Yaeger R, Cuyle PJ, Elez E, Fakih M, Montagut C, Peeters M, Yoshino T, Wasan H, Desai J, Ciardiello F, Gollerkeri A, Christy-Bittel J, Maharry K, Sandor V, Schellens JHM, Kopetz S, Tabernero J. Binimetinib, Encorafenib, and Cetuximab Triplet Therapy for Patients With BRAF V600E-Mutant Metastatic Colorectal Cancer: Safety Lead-In Results From the Phase III BEACON Colorectal Cancer Study. J Clin Oncol. 2019 Jun 10;37(17):1460-1469. doi: 10.1200/JCO.18.02459. Epub 2019 Mar 20. |
Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
| FG002 | Phase 3: Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| FG003 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
| Crossover Participants |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
The baseline analysis population consists of the Full Analysis Set (FAS). For participants in the CSLI, the FAS includes all participants who received at least 1 dose of study drug and had at least 1 post treatment assessment, which may include death. For the randomized Phase 3 portion of the study, the FAS consists of all randomized participants.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Combined Safety Lead-in (CSLI) | Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care. |
| BG001 | Phase 3: Triplet Arm | Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care. |
| BG002 | Phase 3: Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| BG003 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region | Count of Participants | Participants |
| ||||||||||||||||
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) at Baseline | ECOG PS was used to assess the physical health of participants, and ranges from 0 to 5 where 0: fully active, 1: restricted in physically strenuous activity, 2: ambulatory and capable of self-care but unable to work, 3: capable only of limited self-care , 4: completely disabled; cannot carry on any self-care; totally confined to bed or chair, 5: dead. | Count of Participants | Participants |
| |||||||||||||||
| Number of Participants According to Primary Tumor Location | Count of Participants | Participants |
| ||||||||||||||||
| Number of Participants According to Removal of Primary Tumor | Count of Participants | Participants |
| ||||||||||||||||
| Number of Participants According to Number of Organs Involved | Count of Participants | Participants |
| ||||||||||||||||
| Sites of Metastases | One participant may have more than one site of metastases. | Number | Sites |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | (Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs) | The dose-determining set (DDS) consisted of all CSLI participants from the safety set who either completed a minimum exposure requirement (received >= 75% dose intensity of the planned dose for each binimetinib, encorafenib and cetuximab) and had sufficient safety evaluations or experienced a dose-limiting toxicity (DLT). | Posted | Count of Participants | Participants | Cycle 1 (up to 28 days) |
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| Primary | (Safety Lead-in) Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting AEs were reported in this outcome measure. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
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| Primary | (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
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| Primary | (Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis | An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants according to incidence of dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 posttreatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
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| Primary | (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis | OS was defined as the time from randomization to death due to any cause. | The Full Analysis Set (FAS) for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm) |
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| Other Pre-specified | (Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Final Analysis | OS was defined as the time from randomization to death due to any cause. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From randomization to death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Primary | (Phase 3) Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR), where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Safety Lead-in) Objective Response Rate (ORR) by Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Safety Lead-in (SLI) Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Number | 95% Confidence Interval | Percentage of participants | From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Objective Response Rate (ORR) by BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Number | 95% Confidence Interval | Percentage of participants | From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Duration of Response (DOR) by Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Duration of Response (DOR) by BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Time to Response by Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Time to Response by BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Progression-Free Survival (PFS) by Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
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| Secondary | (Safety Lead-in) Progression-Free Survival (PFS) by BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The SLI Efficacy Set consisted of all CSLI participants in the FAS who were identified at screening as having a BRAF V600E mutation (per local or central testing). | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
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| Secondary | (Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm | OS was defined as the time from randomization to death due to any cause. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm) |
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| Secondary | (Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm | OS was defined as the time from randomization to death due to any cause. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 89.1 weeks for triplet arm) |
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| Secondary | (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator | PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. | Posted | Median | 95% Confidence Interval | Months | From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator | ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator | DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Phase 3 Response Efficacy Set consisted of the first 330 participants randomized into the Phase 3 portion of the study and any additional participants randomized on the same day as the 330th randomized participant. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator | Time to response was defined as the time from first dose to first radiographic evidence of response. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
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| Secondary | (Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The EORTC QLQ-C30 questionnaire consisted of 30 questions generating 5 functional scores (physical, role, cognitive, emotional, & social); a global health (GH) status/global quality of life scale score; 3 symptom scale scores (fatigue, pain, & nausea & vomiting); & 6 standalone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, & diarrhea) & perceived financial burden. All items were graded by severity experienced during previous week & used 4-point-scale (1: not at all, 2: a little, 3: quite a bit, 4: very much). The scores were converted to health-related quality of life (HRQoL) scale ranging from 0-100. Higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity). | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. | Posted | Mean | Standard Deviation | Units on a scale | Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
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| Secondary | (Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | FACT-C= Functional Assessment of Chronic Illness Therapy (FACIT), which assessed HRQoL of cancer participants & participants with other chronic illnesses. It consists of total 36 items (27 items of general version of FACT-C and disease-specific subscale containing 9 CRC-specific items), summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range:0-28, emotional well-being (6 items) range: 0-24, colorectal cancer subscale (9 items) range: 0-36; higher subscale score= better QoL. All single-item measures range: 0= 'Not at all' to 4= 'Very much'. Table summarizes functional well-being subscale, individual questions are linearly scaled & combined to form functional well-being subscale score (range 0-28). High score represents better QoL. | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. | Posted | Mean | Standard Deviation | Units on a scale | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
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| Secondary | (Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the participant and ranges from 0 to 100 (higher is better quality health). | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. | Posted | Mean | Standard Deviation | Units on a scale | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
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| Secondary | (Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet | The PGIC is a measure of participant's perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other participant reported outcome (PROs). For this assessment, participants answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse." | The FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants. Here, 'Number Analyzed' signifies number of participants evaluable for the specified timepoints. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. | Posted | Mean | Standard Deviation | Units on a scale | Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab | The pharmacokinetics (PK) set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter *hour | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter *hour | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter *hour | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032) | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter *hour | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032) | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Median | Full Range | Hours | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Median | Full Range | Hours | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Median | Full Range | Hours | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032) | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | Median | Full Range | Hours | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib | The PK set included all participants in the Safety Set who had at least 1 post-dose blood collection for PK with associated bioanalytical results. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram/milliliter | Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
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| Secondary | (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | The analysis set included all participants in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | 95% Confidence Interval | Liter/hour | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
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| Secondary | (Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | The analysis set included all participants in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | 95% Confidence Interval | Liter/hour | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
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| Secondary | (Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab | The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. | The analysis set included all participants in the PK set with measurable plasma concentrations of the test drug plus concentrations from subjects from 4 additional clinical studies. Participants were analyzed according to the actual treatment and dose received. | Posted | Geometric Mean | 95% Confidence Interval | Liter/hour | 2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
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| Secondary | Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to more than or equal to (>=) Grade 3 based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters | Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities | Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: low/high systolic blood pressure (SBP): <= 90 millimeters of mercury (mmHg) with decrease from baseline of >= 20mmHg or >= 160mmHg with increase from baseline of >= 20mmHg, low or high diastolic blood pressure (DBP): <= 50mmHg with decrease from baseline of >= 15mmHg or >= 100mmHg with increase from baseline of >= 15mmHg, low or high pulse: <= 50 beats/min with decrease from baseline of >= 15 beats/min or >= 120 beats/min with increase from baseline of >= 15 beats/min, low or high temperature: <= 36 degree Celsius (deg C) or >= 37.5 deg C. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values | Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: heart rate- decrease from baseline > 25% and to a value < 50 and increase from baseline > 25% and to a value > 100. QT interval- new > 450 (millisecond) msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. QTcF- new > 450 msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score | Visual acuity was measured using the Snellen visual acuity conversion chart. This was determined by establishing the smallest optotypes that could be identified correctly by the participant at a given observation distance. Snellen visual acuity was reported as a Snellen fraction (m/M) in which the numerator (m) indicated the test distance and the denominator (M) indicated the distance at which the gap of the equivalent Landolt ring subtends 1 minute of arc. The LogMAR score was calculated as - log(m/M). The maximum increase in score of <= 0, 0 to < 0.1, 0.1 to < 0.2, 0.2 to < 0.3 and >=0.3 relative to baseline in LogMAR were reported in this endpoint. | The Safety Set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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| Secondary | Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment | Left ventricular ejection fraction (LVEF) abnormalities were defined according to CTCAE version 4.03 where Grade 0: Non-missing value below Grade 2, Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and < -20%, Grade 3: LVEF between 20% and 39% or absolute change from baseline <= -20%, Grade 4: LVEF lower than 20%. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported. | The safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. Participants were analyzed according to treatment received. | Posted | Count of Participants | Participants | From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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Adverse Events (AE) were collected from initiation of study drug through 30 days after the last dose of study drug. For CSLI: maximum treatment exposure of 280 weeks; for Phase 3- Triplet arm: maximum treatment exposure of 277.4 weeks; for Phase 3- Doublet arm: maximum treatment exposure of 268 weeks; for Phase 3- Control arm: maximum treatment exposure of 108 weeks
An AE is defined as the appearance of (or worsening of any pre-existing) undesirable signs, symptoms, or medical conditions that occur after participant's signed informed consent has been obtained. For non-SAEs and SAEs: safety set consisted of all participants who received at least 1 dose of study drug and had at least 1 post-treatment assessment, which may have included death. For all-cause mortality: FAS for the Phase 3 portion of the study consisted of all randomized Phase 3 participants.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combined Safety Lead-in | Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care. | 30 | 37 | 22 | 37 | 36 | 37 |
| EG001 | Phase 3: Triplet Arm | Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care. | 209 | 224 | 118 | 222 | 218 | 222 |
| EG002 | Phase 3: Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. | 193 | 220 | 91 | 216 | 212 | 216 |
| EG003 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. | 198 | 221 | 78 | 193 | 187 | 193 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Gastrointestinal perforation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Intestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Large intestine perforation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Subileus | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Cardio-respiratory arrest | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cerebral ischaemia | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bacteraemia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bile duct obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Large intestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Infusion-related reaction | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal distention | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Duodenal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Haematemesis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| intestinal perforation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pancreatitis relapsing | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rectal stenosis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal hernia | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anal haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Enterocolitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Large intestine ulcer | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Proctalgia | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal wall abscess | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Biliary tract infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cholangitis infective | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Endocarditis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastrintestinal infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Wound abscess | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal abscess | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anal abscess | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Campylobacter gastroenteritis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nephritis | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Death | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anal fistula | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Large intestinal ulcer hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Malabsorption | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Mallory-Weiss syndrome | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Oesophageal ulcer hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Proctitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rectal hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Upper gastrointestinal hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cerebral haematoma | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hepatic encephalopathy | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Tumor haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bile duct obstruction | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bile duct stenosis | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Biliary dilatation | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cholangitis acute | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pericardial effusion | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Clostridial infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Device related sepsis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Enteritis infectious | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Infectious colitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Kidney infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Ophthalmic herpes zoster | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pneumocystis jirovecii pneumonia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pyelonephritis acute | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Staphylococcal bacteraemia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Streptococcal bacteraemia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary tract infection bacterial | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Prerenal failure | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Catheter site thrombosis | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Perforation | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Electrolyte imbalance | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Device occlusion | Product Issues | MedDRA (21.0) | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anastomotic haemorrhage | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anastomotic ulcer | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Radiation inflammation | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rib fracture | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Chondrocalcinosis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Fistula | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Periostitis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Female genital tract fistula | Reproductive system and breast disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Analgesic therapy | Surgical and medical procedures | MedDRA (21.0) | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Jugular vein thrombosis | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Peripheral artery stenosis | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastrointestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastrointestinal ulcer haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Large intestinal haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastrointestinal infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Duodenal perforation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Large intestinal ulcer | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Esophageal ulcer hemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Gastroesophageal reflux disease | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Palmar-planar erythrodysaesthesia | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood creatine increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| White blood cell count decrease | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Retinal detachment | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rhinnorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Tumour Pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Anal haemorrhage | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypertrichosis | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Iron deficiency | Metabolism and nutrition disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Chorioretinopathy | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Macular oedema | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Trichiasis | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Trichomegaly | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Vitreous floaters | Eye disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Restless legs syndrome | Nervous system disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (21.0) | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA (21.0) | Non-systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA (21.0) | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publication until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 23, 2019 | Oct 23, 2023 | SAP_002.pdf |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000601108 | encorafenib |
| C581313 | binimetinib |
| D000068818 | Cetuximab |
| D000077146 | Irinotecan |
| D002955 | Leucovorin |
| D005472 | Fluorouracil |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D002166 | Camptothecin |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Europe |
|
| Rest of World |
|
| 1-Restircted in physically strenuous activity |
|
| 2-Ambulatory and capable of all self-care |
|
| Right Colon |
|
| Left and Right Colon |
|
| Unknown |
|
| Partially Resected/Unresected |
|
| 3+ |
|
| Lung |
|
| Lymph Node |
|
| Peritoneum/Omentum |
|
|
|
|
|
|
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| Participants |
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| Participants |
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| Participants |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Participants |
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| Participants |
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|
|
|
Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
| OG001 | Phase 3:Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3:Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
Encorafenib + binimetinib + cetuximab. Encorafenib: Orally, once daily. Binimetinib: Orally, twice daily. Cetuximab: Standard of care.
| OG001 | Phase 3:Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3:Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
| OG001 | Phase 3:Doublet Arm | Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3:Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3:Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
|
|
|
|
Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
| OG002 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care. |
| OG002 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|
Encorafenib + cetuximab. Encorafenib: Orally, once daily. Cetuximab: Standard of care.
| OG002 | Phase 3: Control Arm | Investigator's choice of either irinotecan/cetuximab or FOLFIRI/cetuximab. Cetuximab: Standard of care. Irinotecan: Standard of care. Folinic Acid: Standard of care. 5-Fluorouracil: Standard of care. Following protocol amendment, eligible participants could crossover to receive either triplet or doublet regimen. |
|
|