Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Other |
(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Final Analysis |
OS was defined as the time from randomization to death due to any cause. |
From randomization to death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Primary |
(Safety Lead-in) Number of Participants With Dose-Limiting Toxicities (DLTs) |
|
Cycle 1 (up to 28 days) |
|
| Primary |
(Safety Lead-in) Number of Participants With Adverse Events (AEs) |
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting AEs were reported in this outcome measure. |
Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
|
| Primary |
(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Interim Analysis |
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. |
Duration of safety lead-in, approximately 6 months (up to 28 days per cycle) |
|
| Primary |
(Safety Lead-in) Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) - Final Analysis |
An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants according to incidence of dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. |
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
|
| Primary |
(Phase 3) Overall Survival (OS) of Triplet Arm vs. Control Arm - Interim Analysis |
OS was defined as the time from randomization to death due to any cause. |
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.1 weeks for triplet arm and 52.4 weeks for control arm) |
|
| Primary |
(Phase 3) Objective Response Rate (ORR) by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 of Triplet Arm vs. Control Arm |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of complete response (CR) or partial response (PR), where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Safety Lead-in) Objective Response Rate (ORR) by Investigator |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Objective Response Rate (ORR) by BICR |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
From start of study treatment until 30 days post last dose of study treatment (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Duration of Response (DOR) by Investigator |
DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Duration of Response (DOR) by BICR |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to the earliest documented PD or death due to underlying disease (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Time to Response by Investigator |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Time to Response by BICR |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Progression-Free Survival (PFS) by Investigator |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Safety Lead-in) Progression-Free Survival (PFS) by BICR |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 280 weeks) |
|
| Secondary |
(Phase 3) Overall Survival (OS) in Doublet Arm vs. Control Arm |
OS was defined as the time from randomization to death due to any cause. |
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 52.4 weeks for control arm) |
|
| Secondary |
(Phase 3) Overall Survival (OS) in Triplet Arm vs. Doublet Arm |
OS was defined as the time from randomization to death due to any cause. |
From randomization to death due to any cause until 204 deaths were observed (maximum treatment exposure of 89.7 weeks for doublet arm and 89.1 weeks for triplet arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Control Arm Per BICR |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-free Survival (PFS) in Triplet Arm vs Control Arm Per Investigator |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per BICR |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-Free Survival (PFS) in Doublet Arm vs Control Arm Per Investigator |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per BICR |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Comparison of Progression-Free Survival (PFS) in Triplet Arm vs Doublet Arm Per Investigator |
PFS was defined as the time from first dose to the earliest documented PD or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From first dose to the earliest documented PD or death due to any cause (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Control Arm Per Investigator |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per BICR |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Phase 3) Comparison of Objective Response Rate (ORR) in Doublet Arm vs Control Arm Per Investigator |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per BICR |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Phase 3) Comparison of Objective Response Rate (ORR) in Triplet Arm vs Doublet Arm Per Investigator |
ORR per RECIST, v1.1, was defined as the percentage of participants achieving an overall best response of CR or PR, where CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis), and PR: at least 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters persistence of one or more non-target lesions and/or maintenance of tumor marker level above the normal limits. |
Duration of Phase 3, approximately 6 months (up to 28 days per cycle) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per BICR |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Control Arm Per Investigator |
DOR was defined as the time from first radiographic evidence of response to the earliest documented disease progression (PD) or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per BICR |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Doublet Arm vs Control Arm Per Investigator |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by BICR |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Comparison of Duration of Response (DOR) in Triplet Arm vs Doublet Arm by Investigator |
DOR was defined as the time from first radiographic evidence of response to the earliest documented PD or death due to underlying disease. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. |
From time of response to PD or death due to underlying disease (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per BICR |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Triplet Arm vs Control Arm Per Investigator |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per BICR |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Doublet Arm vs Control Arm Per Investigator |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 268 weeks for doublet arm and 108 weeks for control arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per BICR |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Comparison of Time to Response in Triplet Arm vs Doublet Arm Per Investigator |
Time to response was defined as the time from first dose to first radiographic evidence of response. |
From first dose to first radiographic evidence of response (maximum treatment exposure of 277.4 weeks for triplet arm and 268 weeks for doublet arm) |
|
| Secondary |
(Phase 3) Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Participants (QLQ-C30) Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet |
The EORTC QLQ-C30 questionnaire consisted of 30 questions generating 5 functional scores (physical, role, cognitive, emotional, & social); a global health (GH) status/global quality of life scale score; 3 symptom scale scores (fatigue, pain, & nausea & vomiting); & 6 standalone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, & diarrhea) & perceived financial burden. All items were graded by severity experienced during previous week & used 4-point-scale (1: not at all, 2: a little, 3: quite a bit, 4: very much). The scores were converted to health-related quality of life (HRQoL) scale ranging from 0-100. Higher scores indicating higher response levels (i.e., higher functioning, higher symptom severity). |
Baseline, Cycle(C)1 Day(D)1 , C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
|
| Secondary |
(Phase 3) Change From Baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet |
FACT-C= Functional Assessment of Chronic Illness Therapy (FACIT), which assessed HRQoL of cancer participants & participants with other chronic illnesses. It consists of total 36 items (27 items of general version of FACT-C and disease-specific subscale containing 9 CRC-specific items), summarized to 5 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items); all 3 subscales range:0-28, emotional well-being (6 items) range: 0-24, colorectal cancer subscale (9 items) range: 0-36; higher subscale score= better QoL. All single-item measures range: 0= 'Not at all' to 4= 'Very much'. Table summarizes functional well-being subscale, individual questions are linearly scaled & combined to form functional well-being subscale score (range 0-28). High score represents better QoL. |
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
|
| Secondary |
(Phase 3) Change From Baseline in the EuroQol-5D-5L Visual Analog Scale (EQ-5D-5L VAS) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet |
The EQ-5D-5L contains 1 item for each of 5 dimensions of health-related QoL (i.e., mobility, self-care, usual activities, pain or discomfort and anxiety or depression). Response options for each item varied from having no problems to moderate problems or extreme problems. The EQ-5D-5L (v4.0) is a standardized measure of health utility that provides a single index value for one's health status. The EQ-5D-5L is frequently used for economic evaluations of health care and has been recognized as a valid and reliable instrument for this purpose. The EQ visual analog scale (VAS) is a score that is directly reported by the participant and ranges from 0 to 100 (higher is better quality health). |
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
|
| Secondary |
(Phase 3) Change From Baseline in the Participant Global Impression of Change (PGIC) in Triplet Arm vs Control Arm, Doublet Arm vs Control, and Triplet vs Doublet |
The PGIC is a measure of participant's perceptions of change in their symptoms over time that can be used as an anchoring method to determine the minimal clinically important difference for other participant reported outcome (PROs). For this assessment, participants answered the following question: "Since starting treatment, my colorectal cancer symptoms are: (1) very much improved, (2) much improved, (3) minimally improved, (4) no change, (5) minimally worse, (6) much worse or (7) very much worse." |
Baseline,Cycle (C)1 Day (D)1, C2 D1, C3 D1, C4 D1, C5 D1, C6 D1, C7 D1, C8 D1, C9 D1, C10 D1, C11 D1, C12 D1, C13 D1, C14 D1, C15 D1, C16 D1, C17 D1, C18 D1, C19 D1, C20 D1, C21 D1, C22 D1, C23 D1, End of Treatment, 30 Day Follow Up(each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Cetuximab |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Encorafenib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Area Under the Concentration-Time Curve From Zero to the Last Measurable Time Point (AUClast) for Binimetinib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Area Under the Concentration-time Curve From Zero to the Last Measurable Time Point (AUClast) for Metabolite of Binimetinib (AR00426032) |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Cetuximab |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Encorafenib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Binimetinib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Maximum Concentration (Cmax) for Metabolite of Binimetinib (AR00426032) |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Cetuximab |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Encorafenib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Binimetinib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Time of Maximum Observed Concentration (Tmax) for Metabolite of Binimetinib (AR00426032) |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Binimetinib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Encorafenib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for Cetuximab |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Safety Lead-in) Evaluation of the Steady-State Concentration Measured Just Before the Next Dose of Study Drug (Ctrough) for a Metabolite of Binimetinib |
|
Predose and 1, 2, 4 and 6 hours post-dose on Day 1 of Cycles 1 and 2 (each cycle of 28 days) |
|
| Secondary |
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Encorafenib |
The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. |
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
|
| Secondary |
(Phase 3) Evaluation of the Model-Based Oral Clearance (CL/F) for Binimetinib |
The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. |
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
|
| Secondary |
(Phase 3) Evaluation of the Model-Based Clearance (CL) for Cetuximab |
The reported cross-arm CL/F value is a fixed-effect parameter determined from a population PK analysis. The analysis included pooled data from participants enrolled in multiple studies including those who were not enrolled in this study. The NCTID include: NCT01719380, NCT01543698, and NCT01436656. An additional study ARRAY-162-105 is not required to register. |
2 and 6 hours post-dose on Day 1 of Cycle 1, Predose and 2 hours post-dose on Day 1 of Cycle 2 (each cycle of 28 days) |
|
| Secondary |
Phase 3: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters |
Clinically notable shifts was defined as worsening by at least 2 grades or to more than or equal to (>=) Grade 3 based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters |
Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Clinically Notable Shifts in Urinalysis Laboratory Parameters |
Clinically notable shifts was defined as worsening by at least 2 grades or to >= Grade 3 based on CTCAE version 4.03 where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life threatening and Grade 5: death. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Newly Occurring Clinically Notable Vital Sign Abnormalities |
Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: low/high systolic blood pressure (SBP): <= 90 millimeters of mercury (mmHg) with decrease from baseline of >= 20mmHg or >= 160mmHg with increase from baseline of >= 20mmHg, low or high diastolic blood pressure (DBP): <= 50mmHg with decrease from baseline of >= 15mmHg or >= 100mmHg with increase from baseline of >= 15mmHg, low or high pulse: <= 50 beats/min with decrease from baseline of >= 15 beats/min or >= 120 beats/min with increase from baseline of >= 15 beats/min, low or high temperature: <= 36 degree Celsius (deg C) or >= 37.5 deg C. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Newly Occurring Clinically Notable Electrocardiogram (ECG) Values |
Newly occurring clinically notable changes was defined as participants not meeting the criterion at baseline and meeting criterion post-baseline. The criterion included: heart rate- decrease from baseline > 25% and to a value < 50 and increase from baseline > 25% and to a value > 100. QT interval- new > 450 (millisecond) msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. QTcF- new > 450 msec, new > 480 msec, new > 500 msec, increase from baseline > 30 msec and increase from baseline > 60 msec. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Shift in Visual Acuity Logarithm of the Minimum Angle of Resolution (LogMAR) Score |
Visual acuity was measured using the Snellen visual acuity conversion chart. This was determined by establishing the smallest optotypes that could be identified correctly by the participant at a given observation distance. Snellen visual acuity was reported as a Snellen fraction (m/M) in which the numerator (m) indicated the test distance and the denominator (M) indicated the distance at which the gap of the equivalent Landolt ring subtends 1 minute of arc. The LogMAR score was calculated as - log(m/M). The maximum increase in score of <= 0, 0 to < 0.1, 0.1 to < 0.2, 0.2 to < 0.3 and >=0.3 relative to baseline in LogMAR were reported in this endpoint. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
|
| Secondary |
Phase 3: Number of Participants With Shifts in Left Ventricular Ejection Fraction (LVEF) From Baseline to Maximum Grade On-treatment |
Left ventricular ejection fraction (LVEF) abnormalities were defined according to CTCAE version 4.03 where Grade 0: Non-missing value below Grade 2, Grade 2: LVEF between 40% and 50% or absolute change from baseline between -10% and < -20%, Grade 3: LVEF between 20% and 39% or absolute change from baseline <= -20%, Grade 4: LVEF lower than 20%. Categories with at least 1 non-zero data values showing any shift in Grade from baseline to 1 day after dose 1 (post-baseline) were reported. Participants whose grade category was unchanged (e.g. Grade 0 to Grade 0) were not reported. |
From start of study treatment until 30 days post last dose of study treatment (for triplet arm: maximum treatment exposure of 277.4 weeks; for doublet arm: maximum treatment exposure of 268 weeks; for Control arm: maximum treatment exposure of 108 weeks) |
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