Metastatic Colorectal Cancer
Conditions
Keywords
MEK162,, panitumumab,, mutant RAS,, wild-type RAS,, metastatic colorectal cancer,, adult mCRC patient
Brief summary
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.
Interventions
DRUGMEK162
Tablet for oral use, 45 mg (three 15 mg tablets), BID
DRUGPanitumumab
Intravenous infusion, 20mg/ml concentrate solution for infusion, Q2W (Days 1 and 15 of every cycle)
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Metastatic colorectal cancer * Progression on or following standard therapy, or no standard therapy (phase Ib). Progression on or following at least 2-prior fluoropyrimidine-containing chemotherapy regimens (phase II) * Written documentation of mutant or wild-type RAS * Life expectancy ≥ 3 months * ECOG performance status ≤ 2
Exclusion criteria
Phase II arms 1 and 4 only: previous treatment with cetuximab, panitumumab, and/or other EGFR inhibitors * Previous treatment with MEK-inhibitors * History of severe infusion reactions to monoclonal antibodies. * Symptomatic or untreated leptomeningeal disease * Symptomatic brain metastasis * Current evidence of retinal disease; history of CSR, RVO or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO and history of keratitis. * Acute or chronic pancreatitis * Clinically significant cardiac disease * Not adequate hematologic, renal and hepatic function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b | Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1) | 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. |
| Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | From the start of the treatment until CR or PR (approximately up to 11 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Electrocardiogram (ECG) Abnormalities | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) | 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. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) | 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. |
| Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b | From the start of the treatment until disease progression (approximately up to 11 months) | 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. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) | 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. |
| Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 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) | 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. |
| Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | From the start of the treatment until disease progression (approximately up to 11 months) | 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. |
| Overall Survival (OS) | From the start of treatment to the date of death due to any cause (approximately up to 11 months) | 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. |
| Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | From the date of randomization to the date of the first documented PD or death (approximately up to 11 months) | 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. |
| Number of Participants With Vital Sign Abnormalities | Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months) | 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. |
Countries
Belgium, Canada, France, Italy, Netherlands, Spain, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 15 |
| 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. | 5 |
| 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. | 15 |
| 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. | 8 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Phase 1b | Death | 2 | 0 | 0 | 0 | 0 |
| Phase 1b | Follow-up completed | 7 | 0 | 0 | 0 | 0 |
| Phase 1b | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
| Phase 2 | Death | 0 | 4 | 0 | 3 | 2 |
| Phase 2 | Disease progression | 0 | 1 | 1 | 1 | 0 |
| Phase 2 | Follow-up completed | 0 | 6 | 3 | 5 | 2 |
| Phase 2 | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Phase 2 | New cancer therapy | 0 | 1 | 0 | 4 | 1 |
| Phase 2 | Participant withdrew consent | 0 | 2 | 1 | 2 | 3 |
Baseline characteristics
| Characteristic | Phase 1b: Binimetinib + Panitumumab | Phase 2: Mutant RAS EGFRi-Naive: Binimetinib + Panitumumab | Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.1 Years STANDARD_DEVIATION 10.6 | 54.3 Years STANDARD_DEVIATION 11.2 | 60.2 Years STANDARD_DEVIATION 12 | 59.8 Years STANDARD_DEVIATION 14 | 54.1 Years STANDARD_DEVIATION 10.7 | 56.4 Years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 4 Participants | 9 Participants | 5 Participants | 31 Participants |
| Sex: Female, Male Male | 6 Participants | 6 Participants | 1 Participants | 6 Participants | 3 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 10 | 15 / 15 | 5 / 5 | 15 / 15 | 8 / 8 |
| serious Total, serious adverse events | 3 / 10 | 6 / 15 | 2 / 5 | 9 / 15 | 5 / 8 |
Outcome results
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.
Time frame: Within the first 28 days of treatment with binimetinib and panitumumab (Cycle 1)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Dose-limiting Toxicities (DLT): Phase 1b | 0 Participants |
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.
Time frame: From the start of the treatment until CR or PR (approximately up to 11 months)
Population: Full analysis set included all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | 0 Percentage of participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | 0 Percentage of participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | 6.7 Percentage of participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 2 | 0 Percentage of participants |
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.
Time frame: From the start of the treatment until disease progression (approximately up to 11 months)
Population: Full analysis set included all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 70.0 Percentage of participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 13.3 Percentage of participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 40.0 Percentage of participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 40.0 Percentage of participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Disease Control Rate (DCR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 37.5 Percentage of participants |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 5.3 Months |
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.
Time frame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
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.
Time frame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >480 msec | 1 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >450 msec | 3 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >60 msec | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >480 msec | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Increase from baseline >30 msec | 3 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Increase from baseline >30 msec | 3 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR decrease >25% and to a VR >100 bpm | 1 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >30 msec | 6 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >450 msec | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: >450 msec | 1 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >500 msec | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR increase >25% and to a VR <50 bpm | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR increase >25% and to a VR <50 bpm | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Increase from baseline >30 msec | 2 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR decrease >25% and to a VR >100 bpm | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >480 msec | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >450 msec | 2 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >30 msec | 3 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >500 msec | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >480 msec | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Increase from baseline >30 msec | 5 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >60 msec | 2 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >450 msec | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: >450 msec | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >450 msec | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >480 msec | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >500 msec | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR decrease >25% and to a VR >100 bpm | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR increase >25% and to a VR <50 bpm | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >450 msec | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >480 msec | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: >450 msec | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >60 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: >450 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR increase >25% and to a VR <50 bpm | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >450 msec | 5 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >450 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >500 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >480 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >480 msec | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >60 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >30 msec | 5 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR decrease >25% and to a VR >100 bpm | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: Increase from baseline >30 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >450 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >480 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR increase >25% and to a VR <50 bpm | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: Increase from baseline >30 msec | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >480 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | Heart rate: RR decrease >25% and to a VR >100 bpm | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >30 msec | 4 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: >450 msec | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcB: >500 msec | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QTcF: >450 msec | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Electrocardiogram (ECG) Abnormalities | QT: increase from baseline >60 msec | 0 Participants |
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.
Time frame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | TEAEs | 10 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | SAEs | 3 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | TEAEs | 15 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | SAEs | 6 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | TEAEs | 5 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | SAEs | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | SAEs | 9 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | TEAEs | 15 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | TEAEs | 8 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAE) | SAEs | 5 Participants |
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.
Time frame: Baseline (Day 1) up to 28 days after last dose of study drug (approximately up to 12 months)
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: high only | 0 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: low only | 1 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: high only | 1 Participants |
| Phase 1b: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: low only | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only | 3 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: low only | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: low only | 0 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: high only | 1 Participants |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: high only | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: high only | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: low only | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: low only | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only | 0 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only | 1 Participants |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: high only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: high only | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: low only | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: low only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only | 2 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: high only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse:>=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: low only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: low only | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Pulse: >=120 bpm or <=50 bpm with increase or decrease from baseline of >=15 bpm: high only | 1 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Oral body temperature: >=39 °C or <=35 °C: high only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | SBP :>=180 mmHg or <=90 mmHg with increase or decrease from baseline of >=20 mmHg: low only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: low only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | DBP: >=105 mmHg or <=50 mmHg with increase or decrease from baseline of >=15 mmHg: high only | 0 Participants |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Number of Participants With Vital Sign Abnormalities | Weight: >=10 % increase or decrease from baseline: high only | 0 Participants |
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.
Time frame: From the start of the treatment until disease progression (approximately up to 11 months)
Population: Full analysis set included all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Overall Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment: Phase 1b | 0 Percentage of participants |
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.
Time frame: From the start of treatment to the date of death due to any cause (approximately up to 11 months)
Population: Full analysis set included all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Overall Survival (OS) | NA Months |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Overall Survival (OS) | 3.5 Months |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Overall Survival (OS) | 5.5 Months |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Overall Survival (OS) | 5.8 Months |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Overall Survival (OS) | 11.2 Months |
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.
Time frame: From the date of randomization to the date of the first documented PD or death (approximately up to 11 months)
Population: Full analysis set included all participants who received at least 1 full or partial dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1b: Binimetinib + Panitumumab | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 3.4 Months |
| Phase 2: Mutant RAS Anti-EGFRi: Binimetinib + Panitumumab | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 1.7 Months |
| Phase 2: WT RAS Anti-EGFRi: Binimetinib + Panitumumab | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 1.8 Months |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 2.4 Months |
| Phase 2: WT RAS EGFRi-Naive: Binimetinib + Panitumumab | Progression-free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Based on Local Radiology Assessment | 2.1 Months |