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| ID | Type | Description | Link |
|---|---|---|---|
| C4211008 | Other Identifier | Alias Study Number | |
| 2013-001986-18 | EudraCT Number |
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The primary purpose of the phase Ib is to estimate the MTD/RPD2 and of the phase II is to assess the anti-tumor activity of MEK162 in combination with panitumumab.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase Ib: Dose escalation | Experimental | Phase Ib: Dose escalation. |
|
| Phase II: Patients with mutant RAS mCRC | Experimental | Patients with mutant RAS mCRC who have not been pretreated with an EGFR inhibitor (EGFRi), including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
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| Phase II: Patients with acquired mutant RAS mCRC | Experimental | Patients with acquired mutant RAS mCRC who have been pretreated with anti-EGFR monoclonal antibody therapy, but have not been pre-treated with EGFR tyrosine kinase inhibitor therapy. |
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| Phase II: Patients with WT RAS mCRC (pretreated) | Experimental | Patients with WT RAS mCRC who have been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
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| Phase II: Patients with WT RAS mCRC (not pretreated) | Experimental | Patients with WT RAS mCRC who have not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MEK162 | Drug | Tablet for oral use, 45 mg (three 15 mg tablets), BID |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b | DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria. | Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1) |
| Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | From the start of the treatment until CR or PR (approximately up to 11 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. |
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Inclusion Criteria:
Exclusion Criteria:
Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors
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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 at Los Angeles Dept of Onc | Los Angeles | California | 90095 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37597246 | Derived | Van Cutsem E, Yaeger R, Delord JP, Tabernero J, Siu LL, Ducreux M, Siena S, Elez E, Kasper S, Zander T, Steeghs N, Murphy D, Edwards M, Wainberg ZA. Phase Ib/II Study of the Efficacy and Safety of Binimetinib (MEK162) Plus Panitumumab for Mutant or Wild-Type RAS Metastatic Colorectal Cancer. Oncologist. 2023 Dec 11;28(12):e1209-e1218. doi: 10.1093/oncolo/oyad210. |
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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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The study used binimetinib 45 mg twice a day (BID) and panitumumab 6 mg/kg intravenous infusion once every second week without planned dose escalation.
Study had Phase 1b followed by Phase 2. Phase 1b was to evaluate the maximum tolerated dose (MTD)/recommended Phase 2 dose (RPD2) in participants with mutant or wild type (WT) rat sarcoma viral oncogene homologue (RAS) metastatic colorectal cancer (mCRC) who had progressed on or following standard therapy or for whom no standard therapy existed. Phase 2 assessed anti-tumor activity in participants enrolled based on the previous anti-EGFR monoclonal antibody therapy and RAS mutational status.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b: Binimetinib (MEK162) + Panitumumab | Participants received binimetinib 45 milligram (mg) orally twice daily with panitumumab 6 milligram per kilogram (mg/kg) intravenous (IV) infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase 1b |
|
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| Panitumumab | Drug | Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle) |
|
| Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
| Number of Participants With Vital Sign Abnormalities | Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): greater than or equal to (>=)180 mmHg or less than equal to (<=) 90 mmHg with increase or decrease from baseline of >=20 mmHg with high and low post baseline values; 2) Diastolic blood pressure (DBP) (mmHg): >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg with high and low post baseline values; 3) Pulse rate in beats per minutes (bpm): >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm with high and low post baseline values; 4) Weight in kilogram: >=10% increase or decrease from baseline with high and low post baseline values; 5) Oral body temperature in degree Celsius (C) : >=39 degree C or <=35 degree C with high and low post baseline values. Categories, with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
| Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (>) 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 3) Heart rate (bpm): RR decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100; RR (interval between 2 successive R waves on ECG) increase >25% and to a VR <50; 4) Pulse rate (msec): increase >25% and to a value >200; 5) QT (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 6) QRS (msec): increase >25% and to a value >110. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Following parameters were analyzed for laboratory examination: hematology (hematocrit, erythrocytes); biochemistry (direct bilirubin, blood urea nitrogen, calcium, creatine kinase, triiodothyronine, thyroxine and thyrotropin). Clinical significance of laboratory abnormalities were judged by investigator. | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
| Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | From the start of the treatment until disease progression (approximately up to 11 months) |
| Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | PFS: time from date of randomization to date of first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD:>=20% increase in sum of diameter of all measured target lesions (TLs), taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm^2. Unequivocal progression of existing non-TLs. Appearance of new lesions. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS was censored at date of last adequate tumor assessment of complete response (CR), partial response (PR) or stable disease (SD). CR:disappearance of all non-nodal TLs/non TLs, any pathological lymph nodes as TLs/non TLs must have reduction in short axis to <10 mm. PR:>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. SD:neither sufficient shrinkage to qualify for PR or CR nor increase in lesions qualified for PD. Kaplan-Meier method used for PFS analysis. | From the date of randomization to the date of the first documented PD or death (approximately up to 11 months) |
| Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | DOR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. RECIST 1.1. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. 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 to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DOR analysis. | From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months) |
| Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | DCR was defined as the percentage of participants with a confirmed BOR of CR, PR, or stable disease (SD). RECIST 1.1, BOR was defined as the best response recorded from the start of the treatment until CR, PR or SD. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. 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^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. | From the start of the treatment until disease progression (approximately up to 11 months) |
| Overall Survival (OS) | OS was defined as the time from the start of treatment to the 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 patient alive. Kaplan-Meier method was used for OS analysis. | From the start of treatment to the date of death due to any cause (approximately up to 11 months) |
| Memorial Sloan Kettering Cancer Center Oncology Dept |
| New York |
| New York |
| 90033 |
| United States |
| Pfizer Investigative Site | Leuven | 3000 | Belgium |
| Pfizer Investigative Site | Toronto | Ontario | M5G 2M9 | Canada |
| Pfizer Investigative Site | Toulouse | 31059 | France |
| Pfizer Investigative Site | Milan | MI | 20162 | Italy |
| Pfizer Investigative Site | Amsterdam | 1066 CX | Netherlands |
| Pfizer Investigative Site | Barcelona | Catalonia | 08035 | Spain |
| FG001 | Phase 2:Mutant RAS Epidermal Growth Factor Receptor Inhibitor(EGFRi)-Naive:Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| FG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| FG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| FG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| COMPLETED |
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| NOT COMPLETED |
|
|
| Phase 2 |
|
|
Full analysis set included all participants who received at least 1 full or partial dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b: Binimetinib + Panitumumab | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. |
| BG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| BG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| BG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| BG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
| BG005 | 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, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b | DLT was defined as an adverse event or clinically significant abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the first 28 days of treatment (Cycle 1) with binimetinib and panitumumab and met any of the specified criteria. | Dose determining set included all phase 1b participants who received at least 1 dose of binimetinib or panitumumab and had at least 1 valid post baseline safety assessment, and those who had either experienced a DLT at any time during Cycle 1 or had met the following minimum treatment and safety evaluation requirements without experiencing a DLT during Cycle 1. | Posted | Count of Participants | Participants | Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1) |
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| Primary | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. | Posted | Number | Percentage of participants | From the start of the treatment until CR or PR (approximately up to 11 months) |
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| Secondary | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. | Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
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| Secondary | Number of Participants With Vital Sign Abnormalities | Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): greater than or equal to (>=)180 mmHg or less than equal to (<=) 90 mmHg with increase or decrease from baseline of >=20 mmHg with high and low post baseline values; 2) Diastolic blood pressure (DBP) (mmHg): >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg with high and low post baseline values; 3) Pulse rate in beats per minutes (bpm): >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm with high and low post baseline values; 4) Weight in kilogram: >=10% increase or decrease from baseline with high and low post baseline values; 5) Oral body temperature in degree Celsius (C) : >=39 degree C or <=35 degree C with high and low post baseline values. Categories, with at least 1 participant having vital sign abnormality in any of the reporting arms, were reported in this outcome measure. | Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
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| Secondary | Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG abnormalities criteria included: 1) QTc interval adjusted according to Bazett formula (QTcB) in millisecond (msec): greater than (>) 450, >480, >500, increase from baseline >30, increase from baseline >60; 2) QTc interval adjusted according to Fridericia formula (QTcF) (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 3) Heart rate (bpm): RR decrease >25% and to a VR (interval between QRS wave and T wave on ECG) >100; RR (interval between 2 successive R waves on ECG) increase >25% and to a VR <50; 4) Pulse rate (msec): increase >25% and to a value >200; 5) QT (msec): >450, >480, >500, increase from baseline >30, increase from baseline >60; 6) QRS (msec): increase >25% and to a value >110. Categories, with at least 1 participant having ECG abnormality in any of the reporting arms, were reported in this outcome measure. | Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. Here, "number analyzed" signifies participants evaluable at specific rows. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
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| Secondary | Number of Participants With Clinically Significant Laboratory Abnormalities | Following parameters were analyzed for laboratory examination: hematology (hematocrit, erythrocytes); biochemistry (direct bilirubin, blood urea nitrogen, calcium, creatine kinase, triiodothyronine, thyroxine and thyrotropin). Clinical significance of laboratory abnormalities were judged by investigator. | Safety analysis set included all participants who received at least 1 full or partial dose of study drug and had at least 1 valid post-baseline safety assessment. | Posted | Count of Participants | Participants | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) |
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| Secondary | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b | ORR: percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) as assessed per RECIST version 1.1. BOR: the best response recorded from the start of the treatment until CR or PR. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. | Posted | Number | Percentage of participants | From the start of the treatment until disease progression (approximately up to 11 months) |
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| Secondary | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | PFS: time from date of randomization to date of first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD:>=20% increase in sum of diameter of all measured target lesions (TLs), taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm^2. Unequivocal progression of existing non-TLs. Appearance of new lesions. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS was censored at date of last adequate tumor assessment of complete response (CR), partial response (PR) or stable disease (SD). CR:disappearance of all non-nodal TLs/non TLs, any pathological lymph nodes as TLs/non TLs must have reduction in short axis to <10 mm. PR:>=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. SD:neither sufficient shrinkage to qualify for PR or CR nor increase in lesions qualified for PD. Kaplan-Meier method used for PFS analysis. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. | Posted | Median | 95% Confidence Interval | Months | From the date of randomization to the date of the first documented PD or death (approximately up to 11 months) |
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| Secondary | Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | DOR: time from first documented occurrence of response (PR or CR) until date of first documented PD or death due to underlying cancer. RECIST 1.1. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. 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 to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. Participants with no PD and were still alive, were censored at last adequate tumor assessment. Kaplan-Meier method was used for DOR analysis. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. The outcome was to be analyzed only in confirmed responders, none of the reporting arms had confirmed responders except Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab. | Posted | Median | 95% Confidence Interval | Months | From the first documented occurrence of response (PR or CR) until the date of the first documented PD or death due to the underlying cancer (approximately up to 11 months) |
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| Secondary | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | DCR was defined as the percentage of participants with a confirmed BOR of CR, PR, or stable disease (SD). RECIST 1.1, BOR was defined as the best response recorded from the start of the treatment until CR, PR or SD. CR: disappearance of all non-nodal target lesions and of all non-target lesions. In addition, any pathological lymph nodes assigned as target lesions/ non-target lesions must have a reduction in short axis to <10 mm. PR: at least a 30 percent (%) decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. 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^2. Unequivocal progression of existing non-target lesions. Appearance of new lesions. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. | Posted | Number | 95% Confidence Interval | Percentage of participants | From the start of the treatment until disease progression (approximately up to 11 months) |
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| Secondary | Overall Survival (OS) | OS was defined as the time from the start of treatment to the 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 patient alive. Kaplan-Meier method was used for OS analysis. | Full analysis set included all participants who received at least 1 full or partial dose of study drug. | Posted | Median | 95% Confidence Interval | Months | From the start of treatment to the date of death due to any cause (approximately up to 11 months) |
|
Baseline up to 28 days after last dose of study drug (approximately up to 12 months)
Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis set included all the participants who received at least 1 dose of study drug and had at least 1 valid post-baseline safety assessment.
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 | Phase 1b: Binimetinib + Panitumumab | Participants received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 40 weeks. | 3 | 10 | 10 | 10 | ||
| EG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. | 6 | 15 | 15 | 15 | ||
| EG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. | 2 | 5 | 5 | 5 | ||
| EG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. | 9 | 15 | 15 | 15 | ||
| EG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. | 5 | 8 | 8 | 8 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Sinus Tachycardia | Cardiac disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Small Intestinal Obstruction | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Abdominal Distension | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Intestinal Obstruction | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| General Physical Health Deterioration | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Skin Infection | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Blood Creatine Phosphokinase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Platelet Count Decreased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Troponin T Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Transient Ischaemic Attack | Nervous system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Acute Kidney Injury | Renal and urinary disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypovolaemic Shock | Vascular disorders | MedDRA v18.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vision Blurred | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Chorioretinopathy | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Retinal Detachment | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Retinopathy | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Periorbital Oedema | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vitreous Floaters | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dry Eye | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Eye Swelling | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Eye Discharge | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Iritis | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Visual Impairment | Eye disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dry Mouth | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Oral Pain | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Gastrointestinal Inflammation | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Rectal Haemorrhage | Gastrointestinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Oedema Peripheral | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Feeling Cold | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Face Oedema | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Facial Pain | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Non-Cardiac Chest Pain | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Peripheral Swelling | General disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Conjunctivitis | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Rash Pustular | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Skin Infection | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Septic Shock | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Stoma Site Pain | Injury, poisoning and procedural complications | MedDRA v18.1 | Non-systematic Assessment |
| |
| Sunburn | Injury, poisoning and procedural complications | MedDRA v18.1 | Non-systematic Assessment |
| |
| Blood Creatine Phosphokinase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Ejection Fraction Decreased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Blood Creatinine Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Lipase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Blood Bilirubin Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Amylase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Blood Alkaline Phosphatase Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Intraocular Pressure Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Troponin Increased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Haemoglobin Decreased | Investigations | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pain In Extremity | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Muscle Spasms | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Neuropathy Peripheral | Nervous system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Retinal Migraine | Nervous system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Genital Haemorrhage | Reproductive system and breast disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vaginal Haemorrhage | Reproductive system and breast disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dyspnoea Exertional | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Nasal Dryness | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pleuritic Pain | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Productive Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dermatitis Acneiform | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Dry Skin | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Skin Fissures | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Skin Ulcer | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hirsutism | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Nail Disorder | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Swelling Face | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Trichorrhexis | Skin and subcutaneous tissue disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA v18.1 | Non-systematic Assessment |
| |
| Fungal Skin Infection | Infections and infestations | MedDRA v18.1 | Non-systematic Assessment |
|
The study used binimetinib 45 mg BID and panitumumab 6 mg/kg intravenous infusion once every second week, there was no planned dose escalation.
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. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C581313 | binimetinib |
| D000077544 | Panitumumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Participant withdrew consent |
|
| Death |
|
| New cancer therapy |
|
| Disease progression |
|
| Follow-up completed |
|
| Male |
|
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab |
Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG002 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG003 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
|
|
Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks.
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
|
|
| OG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
|
|
| OG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
|
|
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
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| OG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
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| OG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
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| OG001 | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with mutant RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 15.4 weeks. |
| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
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| OG002 | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with acquired mutant RAS mCRC who had been pretreated with anti-EGFR monoclonal antibody therapy, but had not been pre-treated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 33.7 weeks. |
| OG003 | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had been pretreated with an anti-EGFRi monoclonal antibody therapy but had not been pretreated with EGFR tyrosine kinase inhibitor therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 32.1 weeks. |
| OG004 | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Participants with WT RAS mCRC who had not been pretreated with an EGFRi, including EGFR tyrosine kinase inhibitor therapy and/or anti-EGFR monoclonal antibody therapy, received binimetinib 45 mg orally twice daily with panitumumab 6 mg/kg IV infusion once every second week on Days 1 and 15 of every cycle (1 cycle = 28 days) until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurred first. Maximum treatment exposure was approximately of 48.0 weeks. |
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