| Primary | Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs) | DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm. | The Dose Determining Set consisted of all SLl phase participants from the Safety Set who either completed a minimum exposure requirement (received at least 75% of the planned dose of each study intervention during Cycle 1) and have sufficient safety evaluations or experienced a DLT. | Posted | | Count of Participants | | Participants | | Cycle 1 (up to 28 days) | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Primary | Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date | PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Primary | Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis | PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR | cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all SLI phase participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator | cORR as determined by investigator assessment per RECIST version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all SLI phase participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Duration of Response (DOR) Per BICR | DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Full Analysis Set consisted of all SLI phase participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Duration of Response (DOR) Per Investigator | DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Full Analysis Set consisted of all SLI phase participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment | Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day". Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen. | The Safety Set consisted of all participants who receive at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Median | Full Range | weeks | | Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting TEAEs were reported in this outcome measure. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Serious TEAEs | A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability. Number of participants reporting serious TEAEs were reported in this outcome measure. | The Safety Set consisted of all participants who receive at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs) | An AE is any untoward medical occurrence in a participant, whether or not considered related to the study intervention. Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities | Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline. The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values | Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline. The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters | Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death. | The Safety Set consisted of all participants who receive at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters | Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities | Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment. [1] The category "Other" includes all other dermatological findings identified during examination (e.g. rash acneiform, skin hyperpigmentation...). | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale | The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale. The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | | First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter (h*ng/mL) | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
|---|
| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
| |
| Secondary | Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
|---|
| OG000 | Safety Lead-in Phase (SLI): ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Prior to the randomized Phase, the Safety Lead-in (SLI) portion was conducted at a limited number of sites to assess the safety and tolerability of the doublet in Chinese homeland participants. |
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| Secondary | Randomized Phase 2: Progression-free Survival (PFS) by Investigator | PFS was defined as the time from the date of randomization to the earliest documented date of PD as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per BICR | cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per Investigator | cORR as determined by investigator assessment per RECIST Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per BICR | DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per Investigator | DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per BICR | cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by BICR per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per Investigator | cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by investigator assesment per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Number | 95% Confidence Interval | percentage of participants | | Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per BICR | TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by BICR per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | | Median | 95% Confidence Interval | months | | From day 1 until first documented response, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per Investigator | TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by investigator assessment per RECIST Version 1.1. CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure. | Posted | | Median | 95% Confidence Interval | months | | From day 1 until first documented response, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Overall Survival (OS) | OS was defined as time from randomization until date of death due to any cause. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Overall Duration of Exposure to Study Treatment | Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day". Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen. | The Safety Set consisted of all participants who receive at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Median | Full Range | weeks | | Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug. Number of participants reporting TEAEs were reported in this outcome measure. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after study intervention discontinuation | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Number of Participants With Serious TEAEs | A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability. Number of participants reporting serious TEAEs were reported in this outcome measure. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after study intervention discontinuation | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities | Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline. The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment | | | | ID | Title | Description |
|---|
| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm |
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| Secondary | Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values | Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline. The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters | Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 |
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| Secondary | Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters | Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03. 'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease. 'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase. Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 |
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| Secondary | Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities | Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment. [1] All other dermatological findings identified during examination (e.g. rash acneiform, skin hyperpigmentation...). | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. Control Arm was not assessed for this outcome as this was performed only for participants receiving encorafenib. | Posted | | Count of Participants | | Participants | | From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale | The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale. The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death. [1] Participants with no assessment of ECOG in the time frame. | The Safety Set consisted of all participants who received at least one dose of study intervention and were analyzed according to treatment received. | Posted | | Count of Participants | | Participants | | Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Time to Definitive Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) Questionnaire Scores | The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire consisted of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale. Each scale in the questionnaire was scored (0 to 100). High scores represented a high health/quality of life. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Time to Definitive Deterioration in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire | The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) consisted of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system consisted of five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each was rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that described the participant's health state. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Time to Definitive Deterioration in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) Questionnaire | The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) was a validated quality of life questionnaire for patient reported outcome assessment. The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) consisted of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale. Higher score reflects a better quality of life. Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Median | 95% Confidence Interval | months | | Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Evolution in the Patient Global Impression of Change (PGIC) Questionnaire | The Patient Global Impression of Change (PGIC) questionnaire is a scale often used to anchor and characterize participant reported outcome (PRO) findings. This consisted of questions that asked participants to evaluate their colorectal cancer symptoms since starting study intervention according to a seven-point verbal rating scale: 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse. Completions of questionnaire are summarized per treatment group and study visits. Number of participants analyzed correspond to the actual number of participants who completed the questionnaire at the corresponding visit. | The Full Analysis Set consisted of all randomized participants who received at least one dose of study intervention. | Posted | | Count of Participants | | Participants | | Cycle 2 Day 1 until 30 days safety follow-up | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly | | OG001 | Randomized Phase: Control Arm | Either Irinotecan and cetuximab, or FOLFIRI and cetuximab Irinotecan: Intravenous infusion of 180 mg/m^2 (90-minute infusion or according to study site standards) every 2 weeks Cetuximab: Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly Folinic acid: Intravenous infusion 400 mg/m^2 (120-minute infusion or according to study site standards) or maximal dose tolerated in a prior regimen, every 2 weeks 5-fluorouracil: Intravenous bolus/intravenous infusion of 400 mg/m^2 initial dose bolus (not to exceed 15 minutes), then 1200 mg/m^2/day x 2 days (total 2400 mg/m^2 over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen, every 2 weeks |
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| Secondary | Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Serum Concentrations of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | hour*nanogram/milliliter | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | The PK Set consisted of all participants who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. No PK analysis was conducted in participants enrolled in Control Arm. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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| Secondary | Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab. | For the Randomized Phase 2, The PK Set consisted of all participants randomized within the ENCO+CETUX Arm, who received at least one dose of encorafenib or cetuximab, and who had at least one post dose PK blood collection with associated bioanalytical results. All participants reported under Overall Number of Participants Analyzed contributed data to the table but may not have evaluable data for every row. Here, "Number Analyzed" signifies participants evaluable for specified rows. | Posted | | Geometric Mean | Geometric Coefficient of Variation | ng/mL | | First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days. | | | | ID | Title | Description |
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| OG000 | Randomized Phase: ENCO + CETUX | Encorafenib (ENCO): 4 x 75 mg oral hard capsule (300 mg total) QD Cetuximab (CETUX): Intravenous infusion of 400 mg/m^2 initial dose (120-minute infusion), then 250 mg/m^2 (60-minute infusion) thereafter, once weekly |
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