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| ID | Type | Description | Link |
|---|---|---|---|
| C4221013 | Other Identifier | Alias Study Number | |
| 2013-004552-38 | EudraCT Number |
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The primary purpose of this study is to assess the anti-tumor activity of LGX818/MEK162 in combination with targeted agents after progression on LGX818/MEK162 combination therapy, as well as the safety and tolerability of the novel triple combinations.
This study consists of two parts: in Part I/Run-In, patients naïve to selective BRAF and MEK inhibitors will be treated with the LGX818/MEK162 combination until disease progression (as defined per RECIST v1.1). Based on the genetic analysis of a tumor biopsy obtained at that time, patients will enter Part II of the study for tailored combination treatment in one of four arms of LGX818/MEK162 + either BKM120, BGJ398, INC280 or LEE011 Patients with BRAF mutant melanoma treated by LGX818/MEK162 combination in other studies can be enrolled directly in Part II of CLGX818X2109 after relapse.
Dose-escalations in the combination arms for which no MTD has been established will be based on the recommendations of a Bayesian logistic regression model guided by an escalation with overdose control criterion
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LGX818 + MEK162 | Experimental |
| |
| LGX818 + MEK162 + LEE011 | Experimental |
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| LGX818 + MEK162 + BGJ398 | Experimental |
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| LGX818 + MEK162 + BKM120 | Experimental |
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| LGX818 + MEK162 + INC280 | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LGX818 | Drug | Combination of LGX818 and MEK162 (Part I) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate (ORR): Part II | ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment. | From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II | DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle (first 21 days for infigratinib and capmatinib; 28 days for ribociclib and buparlisib) of treatment initiation and met the defined criteria for study. |
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INCLUSION CRITERIA:
INCLUSION CRITERIA for triple combinations:
Progressive disease following prior treatment with LGX818/MEK162 combination. PRINCIPAL EXCLUSION CRITERIA Symptomatic or untreated leptomeningeal disease.
Screening/baseline:
Additional exclusion criteria for the triple combinations:
LGX818/MEK162/BKM120:
Investigator or a Psychiatrist:
LGX818/MEK162/BGJ398:
LGX818/MEK162/LEE011:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Los Angeles | Los Angeles | California | 90024 | United States | ||
| Cancer Care Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41914670 | Derived | Dummer R, Sandhu S, Miller WH Jr, Butler MO, Taylor MH, Heinzerling L, Blank CU, Couselo EM, Burris HA 3rd, Postow MA, Chmielowski B, Middleton MR, Berking C, Hassel JC, Gesierich AH, Mauch C, Kleha JF, Polli A, Harney AS, di Pietro A, Ascierto PA. Plain language summary of the LOGIC 2 study: Encorafenib, binimetinib, plus a third drug for people with BRAF V600-mutant melanoma. Future Oncol. 2026 Apr;22(9):995-1013. doi: 10.1080/14796694.2026.2643481. Epub 2026 Mar 31. | |
| 34376578 |
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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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This study had 2 parts. In Part I, 158 participants were enrolled and treated with encorafenib/ binimetinib (LGX818/MEK162) combination until disease progression (PD) [as per RECISTv1.1]. Based on the genetic assessment of a tumor biopsy obtained at PD, participants from Part I entered Part II. In Part II, 58 participants received tailored combination treatment in one of the 4 arms: encorafenib/ binimetinib + buparlisib (BKM120), infigratinib (BGJ398), capmatinib (INC280) or ribociclib (LEE011).
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| ID | Title | Description |
|---|---|---|
| FG000 | Part I: Encorafenib + Binimetinib (Naive) | Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part I |
|
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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 | Dec 16, 2019 | Dec 27, 2023 |
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| MEK162 |
| Drug |
Combination of LGX818 and MEK162 (Part I) |
|
| LEE011 | Drug | Combination of LGX818 + MEK162 + LEE011 (Part II) |
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| BGJ398 | Drug | Combination of LGX818 + MEK162 + BGJ398 (Part II) |
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| BKM120 | Drug | Combination of LGX818 + MEK162 + BKM120 (Part II) |
|
| INC280 | Drug | Combination of LGX818 + MEK162 + INC280 (Part II) |
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| Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib) |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I | An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs. | Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With AEs and SAEs: Part II | An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs. | Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I | Parameters evaluated were: Activated partial thromboplastin time (APTT) (seconds [sec]) - CTCAE graded high, fibrinogen (gram per liter [g/L]) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, prothrombin international normalized ratio (PINR) - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment. | Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II | Parameters evaluated were: APTT (sec) - CTCAE graded high, fibrinogen (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, PINR - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment in Part II. | Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I | Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (units per liter [U/L])- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (micromole per liter [umol/L])- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (millimole per liter [mmol/L])- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. | Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II | Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (U/L)- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L) - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (umol/L)- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (mmol/L)- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. | Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I | Vital signs evaluated were: Low/high systolic blood pressure (BP) (millimeter of Mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (beats per minute [bpm]): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kilogram [kg]): >=20% decrease/increase from baseline; and low/high body temperature (degree Celsius [C]): <=36 C / >= 37.5 C. | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II | Vital signs evaluated were: Low/high systolic BP (mmHg): <=90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (bpm): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kg): >=20% decrease/increase from baseline; and low/high body temperature (C): <=36 C / >= 37.5 C. | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With Notable Electrocardiograms (ECG) Values: Part I | Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: Heart rate (HR): increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 millisecond (ms); QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and Corrected QT interval by Fridericia (QTcF): increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value. | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With Notable ECG Values: Part II | Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: HR: increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 ms; QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and QTcF: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value. | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With At Least One Dose Interruption: Part I | In this outcome measure number of participants with at least 1 dose interruption for encorafenib and binimetinib were reported. | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With At Least One Dose Interruption: Part II | In this outcome measure number of participants with at least 1 dose interruption for encorafenib, binimetinib, and each third combination agent were reported. | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
| Number of Participants With At Least One Dose Reduction: Part I | In this outcome measure number of participants with at least 1 dose reduction for encorafenib and binimetinib were reported. | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
| Number of Participants With At Least One Dose Reduction: Part II | In this outcome measure number of participants with at least 1 dose reduction for encorafenib, binimetinib, and each third combination agent were reported. | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
| Actual Dose Intensity: Part I | Dose intensity across all cycles = cumulative dose/duration of exposure. Treatment cycle for encorafenib and binimetinib =21 days. | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
| Actual Dose Intensity: Part II | Dose intensity = cumulative dose/ duration of exposure. Treatment cycle = 21days for the combination treatment with buparlisib and capmatinib and 28 days for the combination treatment with ribociclib and infigratinib. | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
| Progression-Free Survival (PFS): Part I | PFS was defined as the time from the start date of study drug in Part I until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation. | From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part I was 403.7 weeks) |
| PFS: Part II | PFS was defined as the time from the start date of study drug in Part II until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation. | From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
| Duration of Response (DOR): Part I | DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm. | From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part I was 403.7 weeks) |
| DOR: Part II | DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm. | From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
| Time to Response (TTR): Part I | TTR was defined as the time between the start date of study drug in Part I and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation. | From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part I was 403.7 weeks) |
| TTR: Part II | TTR was defined as the time between the start date of study drug in Part II and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation. | From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part II was 97.0 weeks) |
| Disease Control Rate (DCR): Part I | DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part I was 403.7 weeks) |
| DCR: Part II | DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part II was 97.0 weeks) |
| Overall Survival (OS): Part II | OS was defined as the time from the start date of study treatment (3rd agent combined with encorafenib and binimetinib) to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date participant alive. Kaplan Meier method used for estimation. | From date of start of treatment to date of death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
| Summary of Genomic Biomarkers From Tumor Samples: Part I | Number of participants with multiple alterations in genomic biomarkers like biomarker BRAF, CCND1, CDK4, EGFR, FGFR1, FGFR4, KRAS, MET, NRAS, PIK3CA, and PTEN were reported and alterations included copy number variant/copy number ratio (CNV/CNR), rearrangement, short variant. It was not necessary that all biomarkers had all alterations. Baseline = last non-missing value prior to the first dose of study treatment. | Baseline up to end of treatment (EOT) (maximum treatment exposure for Part I was 403.7 weeks) |
| Plasma Concentration for Encorafenib (LGX): Part I | In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5) and end of treatment (EOT). Maximum treatment exposure for Part I was of 403.7 weeks. | C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT |
| Plasma Concentration for Encorafenib (LGX): Part II | In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 16 (D16), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5). Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
| Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I | AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part I was of 403.7 weeks. | C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT |
| Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II | AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
| Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II | LEQ803 is metabolite of ribociclib. Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
| Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II | BHS697 and CQM157 are metabolites of infigratinib. Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; EOT |
| Plasma Concentration for Capmatinib (INC): Part II | Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
| Plasma Concentration for Buparlisib (BKM): Part II | Maximum treatment exposure for Part II was of 97.0 weeks. | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
| Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | C1 D15: 0.5 hour ± 10 (minutes) min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II | Elimination half-life means the time required for the plasma concentration to decline by 50% during the elimination phase. | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state. | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | C1 D15: at the end of a dosing interval at steady-state (24 hour ± 2 hour), taken directly before next administration |
| Los Angeles |
| California |
| 90095 |
| United States |
| Doris Stein Research Center Building | Los Angeles | California | 90095 | United States |
| Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services | Los Angeles | California | 90095 | United States |
| UCLA Dermatology Clinic | Los Angeles | California | 90095 | United States |
| UCLA Oncology Center | Los Angeles | California | 90095 | United States |
| UCLA Radiology | Los Angeles | California | 90095 | United States |
| Memorial Sloan Kettering Cancer Center Attn: Geny O'neill | New York | New York | 10065 | United States |
| Memorial Sloan Kettering Cancer Center Inpatient Hospital & Main Campus | New York | New York | 10065 | United States |
| Memorial Sloan Kettering Cancer Center- Outpatient Clinic | New York | New York | 10065 | United States |
| OHSU Knight Cancer Institute | Portland | Oregon | 97201 | United States |
| OHSU Center for Health and Healing 2 | 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 |
| Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Tennessee Oncology, PLLC | Nashville | Tennessee | 37203 | United States |
| Peter MacCallum Cancer Centre | Melbourne | Victoria | 3000 | Australia |
| East St Kilda Eye Clinic | Melbourne | Victoria | 3183 | Australia |
| Princess Margaret Cancer Center | Toronto | Ontario | M5G 2M9 | Canada |
| Sir Mortimer B. Davis-Jewish General Hospital | Monteral | Quebec | H3T 1E2 | Canada |
| University Clinic Heidelberg PPDS | Heidelberg | Baden-Wurttemberg | 69120 | Germany |
| Universitätsklinikum Würzburg | Würzburg | Bavaria | 97080 | Germany |
| Uniklinik Köln | Cologne | 50937 | Germany |
| Städtisches Klinikum München | München | 80337 | Germany |
| Universitätsklinikum Würzburg | Würzburg | 97080 | Germany |
| Azienda Ospedaliera Monaldi | Naples | Campania | 80131 | Italy |
| U.O.C. Oncologia Medica e Terapie Innovative Dipartimento di Melanoma IRCCS Fondazione G. Pascale | Naples | 80131 | Italy |
| Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis | Amsterdam | 1066 CX | Netherlands |
| Hospital Universitario Vall d'Hebrón - PPDS | Barcelona Cataluna | Barcelona | 08035 | Spain |
| Universitätsspital Zürich | Zurich Flughafen | 8058 | Switzerland |
| Churchill Hospital | Oxford | OX2 7JL | United Kingdom |
| Derived |
| Nassar KW, Hintzsche JD, Bagby SM, Espinoza V, Langouet-Astrie C, Amato CM, Chimed TS, Fujita M, Robinson W, Tan AC, Schweppe RE. Targeting CDK4/6 Represents a Therapeutic Vulnerability in Acquired BRAF/MEK Inhibitor-Resistant Melanoma. Mol Cancer Ther. 2021 Oct;20(10):2049-2060. doi: 10.1158/1535-7163.MCT-20-1126. Epub 2021 Aug 10. |
| FG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
| FG002 | Part II: Encorafenib + Binimetinib + Ribociclib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| FG003 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| FG004 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| FG005 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Part II |
|
|
Analysis population: participants who were treated with at least 1 dose (partial or full) of encorafenib or binimetinib in Part I and at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment in Part II. Parts I and II participants are not exclusive. To avoid risk of identification of participant, baseline measure data is not disclosed for reporting arm including Infigratinib and reported under category- Not Disclosed.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Part I: Encorafenib + Binimetinib (Naive) | Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment. |
| BG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
| BG002 | Part II: Encorafenib + Binimetinib + Ribociclib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| BG003 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| BG004 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| BG005 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
| BG006 | 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, Customized | Data for arm - Part II: Encorafenib + Binimetinib + Infigratinib is not disclosed to avoid risk of identification and kept under category Not disclosed category. | Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive. | Count of Participants | Participants |
| |||||||||
| Sex/Gender, Customized | Data for arm - Part II: Encorafenib + Binimetinib + Infigratinib is not disclosed to avoid risk of identification and kept under category Not disclosed category. | Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive. | Count of Participants | Participants |
| |||||||||
| Race/Ethnicity, Customized | Race is reported. Data for arm - Part II: Encorafenib + Binimetinib + Infigratinib is not disclosed to avoid risk of identification and kept under category Not disclosed category. | Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive. | Count of Participants | Participants |
| |||||||||
| Race/Ethnicity, Customized | Ethnicity is reported. Data for arm - Part II: Encorafenib + Binimetinib + Infigratinib is not disclosed to avoid risk of identification and kept under category Not disclosed category. | Number Analyzed for Part I and Part II = number of participants analyzed for reporting arms for respective parts. Part I and Part II participants are not exclusive. | Count of Participants | Participants |
|
| 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 | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Response Rate (ORR): Part II | ORR: percentage of participants with confirmed complete response (CR) and partial response (PR). Response evaluation criteria in solid tumors (RECIST) v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions that had a reduction in short axis to less than (<) 10 millimeter (mm). Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Any radiological assessments taken more than 30 days after the last dose of study therapy or after antineoplastic agents other than study treatments taken by the participants was excluded from the best overall response derivation. Confirmation of CR or PR was to be at least 4 weeks apart from the previous radiological assessment. | For Part II, full analysis set (FAS) consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. | Posted | Number | 95% Confidence Interval | Percentage of participants | From the start of the treatment until disease/clinical progression or death or early study discontinuation, whichever happened earlier (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With Dose Limiting Toxicities (DLTs) in Cycle 1: Part II | DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first cycle (first 21 days for infigratinib and capmatinib; 28 days for ribociclib and buparlisib) of treatment initiation and met the defined criteria for study. | Dose-determining analysis set (DDS) consisted of all participants from the safety set for Part II who met the minimum requirements for safety evaluation and minimum exposure or experienced DLT during the first cycle of the assigned triple combination treatment. No participants were included in the dose-determining analysis set in the encorafenib/binimetinib+ infigratinib or buparlisib arm, hence no participants analyzed for these reporting arms for this outcome measure. | Posted | Count of Participants | Participants | Cycle 1 (21 days following the first dose of the combination treatment with buparlisib and capmatinib; 28 days for the combination with ribociclib and infigratinib) |
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| Secondary | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs): Part I | An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With AEs and SAEs: Part II | An AE was defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after participants' signed informed consent has been obtained. An SAE was an AE resulting in any of the following outcomes: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. AEs included both SAEs and all Non-SAEs. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Day 1 up to 30 days after last dose (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With Worst Post-baseline Hematology Results Based on Common Terminology Criteria for Adverse Events (CTCAE) v4.03 Grade: Part I | Parameters evaluated were: Activated partial thromboplastin time (APTT) (seconds [sec]) - CTCAE graded high, fibrinogen (gram per liter [g/L]) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, prothrombin international normalized ratio (PINR) - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With Worst Post-baseline Hematology Results Based on CTCAE v4.03 Grade: Part II | Parameters evaluated were: APTT (sec) - CTCAE graded high, fibrinogen (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded low, hemoglobin (g/L) - CTCAE graded high, PINR - CTCAE graded high, lymphocytes (10^9 cells/L) - CTCAE graded low, lymphocytes (10^9 cells/L) - CTCAE graded high, neutrophils (10^9 cells/L) - CTCAE graded low, platelets (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded low, leukocytes (10^9 cells/L) - CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. Baseline = last non-missing value prior to the first dose of study treatment in Part II. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part I | Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (units per liter [U/L])- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (micromole per liter [umol/L])- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (millimole per liter [mmol/L])- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline up to last dose (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With Worst Post-baseline Serum Chemistry Results Based on CTCAE v4.03 Grade: Part II | Parameters evaluated were: albumin (g/L)- CTCAE graded low, alkaline phosphatase (U/L)- CTCAE graded high, alanine aminotransferase (U/L)- CTCAE graded high, amylase (U/L) - CTCAE graded high, aspartate aminotransferase(U/L)- CTCAE graded high, bilirubin (umol/L)- CTCAE graded high, creatinine (umol/L) - CTCAE graded high, creatine kinase (U/L)- CTCAE graded high, gamma glutamyl transferase (U/L)- CTCAE graded high, glucose (mmol/L)- CTCAE graded low, high, potassium (mmol/L)- CTCAE graded low, potassium (mmol/L)- CTCAE graded high, magnesium (mmol/L)- CTCAE graded low, high, phosphate (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded low, sodium (mmol/L)- CTCAE graded high, urate (umol/L)- CTCAE graded high. CTCAE version 4.03 was used: grade 1 = mild, grade 2 = moderate, grade 3 = severe, grade 4 = life-threatening consequences; grade 0 = values not meeting any of the criteria for grade 1 or higher. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline up to last dose (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part I | Vital signs evaluated were: Low/high systolic blood pressure (BP) (millimeter of Mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (beats per minute [bpm]): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kilogram [kg]): >=20% decrease/increase from baseline; and low/high body temperature (degree Celsius [C]): <=36 C / >= 37.5 C. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. 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 number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With Newly Occurring Notably Abnormal Vital Signs: Part II | Vital signs evaluated were: Low/high systolic BP (mmHg): <=90 mmHg with decrease from baseline of >=20 mmHg / >=160 mmHg with increase from baseline of >=20 mmHg; low/high diastolic BP [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg / >=100 mmHg with increase from baseline of >=15 mmHg; low/high pulse rate (bpm): <=50 bpm with decrease from baseline of >=15 bpm / >=120 bpm with increase from baseline of >=15 bpm; low/high weight (kg): >=20% decrease/increase from baseline; and low/high body temperature (C): <=36 C / >= 37.5 C. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. 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 number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With Notable Electrocardiograms (ECG) Values: Part I | Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: Heart rate (HR): increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 millisecond (ms); QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and Corrected QT interval by Fridericia (QTcF): increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. 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 number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With Notable ECG Values: Part II | Number of participants with notable ECG values were reported in this outcome measure. Abnormality categories were: HR: increase from baseline >25% and to a value >100 bpm, decrease from baseline >25% and to a value <60 bpm; PR: increase from baseline >25% and to a value >200 ms; QRS: increase from baseline >25% and to a value >110 ms; QT: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms; and QTcF: increase from baseline >30 ms, increase from baseline >60 ms, new interval >450 ms, new interval >480 ms, new interval >500 ms. New = newly occurred post-baseline value. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. 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 number of participants evaluable for specified rows. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With At Least One Dose Interruption: Part I | In this outcome measure number of participants with at least 1 dose interruption for encorafenib and binimetinib were reported. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With At Least One Dose Interruption: Part II | In this outcome measure number of participants with at least 1 dose interruption for encorafenib, binimetinib, and each third combination agent were reported. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified treatment in the respective reporting arms. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Number of Participants With At Least One Dose Reduction: Part I | In this outcome measure number of participants with at least 1 dose reduction for encorafenib and binimetinib were reported. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Number of Participants With At Least One Dose Reduction: Part II | In this outcome measure number of participants with at least 1 dose reduction for encorafenib, binimetinib, and each third combination agent were reported. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified treatment in the respective reporting arms. | Posted | Count of Participants | Participants | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Actual Dose Intensity: Part I | Dose intensity across all cycles = cumulative dose/duration of exposure. Treatment cycle for encorafenib and binimetinib =21 days. | Safety set included all participants who received at least 1 dose of encorafenib or binimetinib for Part I and had at least 1 valid post-baseline safety assessment. | Posted | Mean | Standard Deviation | Milligram per day | During study treatment (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Actual Dose Intensity: Part II | Dose intensity = cumulative dose/ duration of exposure. Treatment cycle = 21days for the combination treatment with buparlisib and capmatinib and 28 days for the combination treatment with ribociclib and infigratinib. | Safety set included all participants who received at least 1 dose of 3rd combination agent for Part II and had at least 1 valid post-baseline safety assessment. Here, "Number Analyzed" signifies number of participants evaluable for specified drug. | Posted | Mean | Standard Deviation | Milligram per day | During study treatment (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Progression-Free Survival (PFS): Part I | PFS was defined as the time from the start date of study drug in Part I until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation. | For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. | Posted | Median | 95% Confidence Interval | Months | From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | PFS: Part II | PFS was defined as the time from the start date of study drug in Part II until documented PD or death due to any cause. All participants who had not progressed or died at the time of the data cut-off were censored at the date of last tumor assessment (other than those who were unknown or missing) prior to cut-off date or start date of new anti-neoplastic therapy, whichever is earlier. Per RECIST 1.1, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan Meier method used for estimation. | For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. | Posted | Median | 95% Confidence Interval | Months | From start of study drug until documented PD or death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Duration of Response (DOR): Part I | DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm. | For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were confirmed responders. Kaplan Meier method used for estimation. | Posted | Median | 95% Confidence Interval | Months | From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | DOR: Part II | DOR: time between date of first documented response (CR or PR) and date of first documented progression or death due to underlying cancer. If there was no progression or death due to underlying cancer, then the participant was censored at the date of last tumor assessment other than unknown. RECIST v1.1: CR = disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. All lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) PD= At least a 20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition, sum must also demonstrate an absolute increase of at least 5 mm. | For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were confirmed responders. Kaplan Meier method used for estimation. | Posted | Median | 95% Confidence Interval | Months | From date of first documented response (CR or PR) till the date of first documented progression or death due to underlying cancer or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Time to Response (TTR): Part I | TTR was defined as the time between the start date of study drug in Part I and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation. | For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were responders. | Posted | Median | 95% Confidence Interval | Months | From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | TTR: Part II | TTR was defined as the time between the start date of study drug in Part II and first documented response (CR or PR). RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis) and b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Kaplan Meier method used for estimation. | For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure who were responders. | Posted | Median | 95% Confidence Interval | Months | From start date of study drug till first documented response (CR or PR) (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Disease Control Rate (DCR): Part I | DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. | Posted | Number | 95% Confidence Interval | Percentage of participants | From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | DCR: Part II | DCR was defined as percentage of participants with a best overall response of CR or PR or SD. RECIST v1.1: a) CR = disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must had a reduction in short axis to <10 mm. Disappearance of all non-target lesions. In addition, all lymph nodes assigned a non-target lesion must be non-pathological in size (<10 mm short axis); b) PR = at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters and c) SD = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. | Posted | Number | 95% Confidence Interval | Percentage of participants | From start date of study drug till first documented response (CR or PR or SD) (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Overall Survival (OS): Part II | OS was defined as the time from the start date of study treatment (3rd agent combined with encorafenib and binimetinib) to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date participant alive. Kaplan Meier method used for estimation. | For Part II, FAS consisted of all participants who received at least 1 dose of encorafenib or binimetinib or the assigned third agent following the assignment of the triple combination treatment. | Posted | Median | 95% Confidence Interval | Months | From date of start of treatment to date of death due to any cause or censoring date (maximum treatment exposure for Part II was 97.0 weeks) |
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| Secondary | Summary of Genomic Biomarkers From Tumor Samples: Part I | Number of participants with multiple alterations in genomic biomarkers like biomarker BRAF, CCND1, CDK4, EGFR, FGFR1, FGFR4, KRAS, MET, NRAS, PIK3CA, and PTEN were reported and alterations included copy number variant/copy number ratio (CNV/CNR), rearrangement, short variant. It was not necessary that all biomarkers had all alterations. Baseline = last non-missing value prior to the first dose of study treatment. | For Part I, FAS consisted of all participants who received at least 1 dose (partial or full) of encorafenib or binimetinib. | Posted | Count of Participants | Participants | Baseline up to end of treatment (EOT) (maximum treatment exposure for Part I was 403.7 weeks) |
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| Secondary | Plasma Concentration for Encorafenib (LGX): Part I | In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5) and end of treatment (EOT). Maximum treatment exposure for Part I was of 403.7 weeks. | Pharmacokinetic analysis set (PAS) consisted of all participants who had at least one blood sample providing evaluable pharmacokinetic (PK) data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT |
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| Secondary | Plasma Concentration for Encorafenib (LGX): Part II | In results reported below, following abbreviation have been used: Cycle 1 (C1), Day 1 (D1), Day 8 (D8), Day 15 (D15), Day 16 (D16), Day 21 (D21), Cycle 2 (C2), Cycle 3 (C3), Cycle 4 (C4), Cycle 5 (C5). Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
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| Secondary | Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part I | AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part I was of 403.7 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5 hrs post-dose on D1; pre-dose, 1.5 hrs post-dose on D15); C2 (pre-dose on D8 and D21); C3 pre-dose on D15; C4 pre-dose on D15; C5 pre-dose on D15; EOT |
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| Secondary | Plasma Concentration for Binimetinib (MEK) and Its Metabolite: Part II | AR00426032 is metabolite of binimetinib. Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
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| Secondary | Plasma Concentration for Ribociclib (LEE) and Its Metabolite: Part II | LEQ803 is metabolite of ribociclib. Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5, 4 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
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| Secondary | Plasma Concentration for Infigratinib (BGJ) and Its Metabolites: Part II | BHS697 and CQM157 are metabolites of infigratinib. Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6 hrs post-dose on D15; 24 hrs post-dose on D16; pre-dose on D21); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; EOT |
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| Secondary | Plasma Concentration for Capmatinib (INC): Part II | Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under 'Overall Number of Participants Analyzed' contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
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| Secondary | Plasma Concentration for Buparlisib (BKM): Part II | Maximum treatment exposure for Part II was of 97.0 weeks. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified time points. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 (1.5 hrs post-dose on D1; pre-dose on D8; pre-dose, 0.5, 1.5, 2.5, 4, 6, 8 hrs post-dose on D15; 24 hrs post-dose on D16); C2 (pre-dose on D1 and D15); C3 pre-dose on D1; C4 pre-dose on D1; C5 pre-dose on D1; EOT |
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| Secondary | Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 D15: 0.5 hour ± 10 (minutes) min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
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| Secondary | Time to Reach Cmax at Steady State (Tmax, ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Median | Full Range | Hour | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
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| Secondary | Area Under the Concentration-time Curve From Time Zero to Time Tau at Steady-State (AUCtau,ss) for Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour*nanogram per milliliter | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
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| Secondary | Elimination Half-life at Steady State (t1/2, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Capmatinib, and Buparlisib: Part II | Elimination half-life means the time required for the plasma concentration to decline by 50% during the elimination phase. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Mean | Standard Deviation | Hour | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
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| Secondary | Apparent Total Plasma Clearance at Steady State (Cl, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
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| Secondary | Apparent Volume of Distribution at Steady State (Vz, ss/F) of Encorafenib, Binimetinib, Ribociclib, Capmatinib, and Buparlisib: Part II | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution is the apparent volume of distribution at steady-state. | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Last Measurable Plasma Concentration at Steady State (Clast, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 D15: 0.5 hour ± 10 min; 1 hour ± 10 min; 1.5 hour ± 15 min; 2 hour ± 15 min; 2.5 hour ± 15 min; 4 hour ± 30 min; 6 hour ± 30 min; 8 hour ± 60 min; 24 hour ± 2 hour |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Measured Concentration at the End of a Dosing Interval at Steady State (Ctrough, ss) of Encorafenib, Binimetinib, Binimetinib Metabolite, Ribociclib, Ribociclib Metabolite, Infigratinib, Infigratinib Metabolites, Capmatinib, and Buparlisib: Part II | PAS consisted of all participants who had at least one blood sample providing evaluable PK data. All participants reported under "Number of Participants Analyzed" contributed data to the table; however, may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants evaluable for specified study treatment or metabolites for respective arms. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram per milliliter | C1 D15: at the end of a dosing interval at steady-state (24 hour ± 2 hour), taken directly before next administration |
|
Day 1 up to 30 days after last dose (maximum treatment exposure for Part I was 403.7 weeks and for Part II was 97.0 weeks)
Same event may appear as both non-SAE and SAE, but what is presented are distinct events. An event may be categorized as serious in 1 participant and non-serious in other participant, or a participant may have experienced both SAE and non-SAE. Safety set evaluated.
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 | Part I: Encorafenib + Binimetinib (Naive) | Participants naive to selective V-raf murine sarcoma viral oncogene homolog B1 (BRAF) and mitogen-activated protein kinase (MEK) inhibitors, received encorafenib 450 milligram (mg) once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for encorafenib and binimetinib was defined as 21 days of daily continuous treatment. | 20 | 75 | 47 | 75 | 75 | 75 |
| EG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. | 29 | 83 | 37 | 83 | 73 | 83 |
| EG002 | Part II: Encorafenib + Binimetinib + Ribociclib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and ribociclib 100 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For ribociclib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Ribociclib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. | 28 | 38 | 19 | 38 | 33 | 38 |
| EG003 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. | 1 | 1 | 0 | 1 | 0 | 1 |
| EG004 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. | 8 | 13 | 6 | 13 | 11 | 13 |
| EG005 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. | 4 | 6 | 4 | 6 | 5 | 6 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cardiac arrest | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Adrenomegaly | Endocrine disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Adrenocortical insufficiency acute | Endocrine disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diplopia | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Exophthalmos | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Colitis ulcerative | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Intestinal mass | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Intussusception | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Intestinal perforation | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Subileus | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Terminal ileitis | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Disease progression | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Arthritis bacterial | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chorioretinitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Clostridium difficile colitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Erysipelas | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Febrile infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Streptococcal infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urosepsis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vestibular neuronitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Osteoradionecrosis | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Periprosthetic fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Procedural pneumothorax | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Seroma | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Intraocular pressure increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Troponin T increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Fibromyalgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myopathy toxic | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Breast cancer recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Metastases to spine | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Tumour ulceration | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Aphasia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Embolic cerebral infarction | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hemiplegia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Paraparesis | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Paresis | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Partial seizures | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pulmonary alveolar haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Shock | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Subretinal fluid | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Visual field defect | Eye disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatine increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA version 25.0 | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA version 25.0 | Non-systematic Assessment |
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Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications 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. | 1-800-718-102 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2023 | Dec 27, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000601108 | encorafenib |
| C581313 | binimetinib |
| C000589651 | ribociclib |
| C568950 | infigratinib |
| C571178 | NVP-BKM120 |
| C000613976 | capmatinib |
Not provided
Not provided
Not provided
| Death |
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| Progressive Disease |
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| New Therapy for Study Indication |
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| Physician Decision |
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| Participant/Guardian Decision |
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| Part II |
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| Part II |
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| Race: Part II |
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| Ethnicity: Part II |
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| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
|
|
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
|
|
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
|
|
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 |
| Part I: Encorafenib + Binimetinib (Non-naive) |
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part I: Encorafenib + Binimetinib (Non-naive) | Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG001 | Part II: Encorafenib + Binimetinib + Infigratinib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and infigratinib 75 mg (starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For infigratinib dose escalation was allowed till 125 mg and dose reduction was permitted till 25 mg. Infigratinib was taken for 21 consecutive days followed by a 7-day planned break. Treatment cycle =28 days. |
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
| OG002 | Part II: Encorafenib + Binimetinib + Capmatinib | Participants, received encorafenib 200 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and capmatinib 200 mg (starting dose) capsule or 400 mg (starting dose) tablet twice a day until disease progression or no clinical benefit. No dose reduction below 50 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For capmatinib dose escalation was allowed till 600 mg and dose reduction was permitted till 50 mg. Treatment cycle for encorafenib, binimetinib and capmatinib was defined as 21 days of daily continuous treatment. |
| OG003 | Part II: Encorafenib + Binimetinib + Buparlisib | Participants, received encorafenib 450 mg (starting dose) once a day, binimetinib 45 mg (starting dose) twice a day and buparlisib 60 mg starting dose) once a day until disease progression or no clinical benefit. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. For buparlisib dose escalation was allowed till 100 mg and dose reduction was permitted till 30 mg. Treatment cycle for encorafenib, binimetinib and buparlisib was defined as 21 days of daily continuous treatment. |
|
|
|
|
Participants non-naive to selective BRAF and MEK inhibitors, received encorafenib 450 mg once a day and binimetinib 45 mg twice a day until disease progression or no clinical benefit and initiation of triple combination treatment. No dose reduction below 150 mg for encorafenib and 15 mg for binimetinib was permitted for this study. Treatment cycle for both drugs was defined as 21 days of daily continuous treatment. |
|
|
| OG002 |
| Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Infigratinib 75 mg |
Participants received encorafenib 450 mg once a day and binimetinib 45 mg twice a day along with infigratinib 75 mg once a day. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 200 mg twice a day. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 300 mg twice a day. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with capmatinib 400 mg twice a day. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 400 mg once a day. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg once a day and binimetinib 30 mg twice a day along with ribociclib 600 mg once a day. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 400 mg once a day. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg once a day and binimetinib 45 mg twice a day along with ribociclib 600 mg once a day. |
|
|
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG012 | Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG005 | Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG006 | Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
|
|
|
Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID.
|
|
| Participants |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD.
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD.
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
| OG002 |
| Part II: Encorafenib 450 mg/ Binimetinib 45 mg + Infigratinib 75 mg |
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD. |
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD.
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
Participants received encorafenib 450 mg QD and binimetinib 45 mg BID and infigratinib 75 mg QD.
| OG003 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 200 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 200 mg BID. |
| OG004 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 300 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 300 mg BID. |
| OG005 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Capmatinib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and capmatinib 400 mg BID. |
| OG006 | Part II: Encorafenib 100 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 100 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG007 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 400 mg QD. |
| OG008 | Part II: Encorafenib 200 mg/ Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
| OG009 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 400 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 400 mg QD. |
| OG010 | Part II: Encorafenib 200 mg/ Binimetinib 45 mg + Ribociclib 600 mg | Participants received encorafenib 200 mg QD and binimetinib 45 mg BID and ribociclib 600 mg QD. |
| OG011 | Part II: Encorafenib 300 mg/Binimetinib 30 mg + Ribociclib 600 mg | Participants received encorafenib 300 mg QD and binimetinib 30 mg BID and ribociclib 600 mg QD. |
|
|
| 45-64 years |
|
| 65 years and over |
|
| Not disclosed |
|
| Male |
|
| Not Disclosed |
|
| Asian |
|
| Not Disclosed |
|
| Not Hispanic or Latino |
|
| Not Disclosed |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
|
| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
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| Worst post-baseline value Grade 2 |
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| Worst post-baseline value Grade 3 |
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| Worst post-baseline value Grade 4 |
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| Worst post-baseline value Missing |
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| Worst post-baseline value Grade 1 |
|
| Worst post-baseline value Grade 2 |
|
| Worst post-baseline value Grade 3 |
|
| Worst post-baseline value Grade 4 |
|
| Worst post-baseline value Missing |
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