A Study of Encorafenib Plus Cetuximab With or Without Chemotherapy in People With Previously Untreated Metastatic Colorectal Cancer

Recruitment Status
ACTIVE, NOT RECRUITING - HAS RESULTS
(See Contacts and Locations)Verified April 2026 by Pfizer
Sponsor
Pfizer
Information Provided by (Responsible Party)
Pfizer
Clinicaltrials.gov Identifier
NCT04607421
Other Study ID Numbers:
C4221015
First Submitted
October 4, 2020
First Posted
October 28, 2020
Results First Posted
February 25, 2026
Last Update Posted
June 10, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on May 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

The purpose of the study is to evaluate whether encorafenib plus cetuximab (EC), alone or in combination with chemotherapy, can improve clinical outcomes relative to current standard of-care chemotherapy in participants with previously untreated BRAF V600E-mutant mCRC. Since encorafenib has not previously been combined with chemotherapy, the tolerability and PK of EC in combination with mFOLFOX6 and in combination with FOLFIRI will be evaluated in separate cohorts in the safety lead-in portion of the trial in order to identify which chemotherapy combination is to be used in the Phase 3 portion of the study.

Condition or DiseaseIntervention/Treatment
Neoplasms
Drug: EncorafenibDrug: EncorafenibDrug: EncorafenibDrug: EncorafenibDrug: OxaliplatinDrug: EncorafenibDrug: Irinotecan

Study Design

Study TypeInterventional
Actual Enrollment841 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleAN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE 3 STUDY OF FIRST-LINE ENCORAFENIB PLUS CETUXIMAB WITH OR WITHOUT CHEMOTHERAPY VERSUS STANDARD OF CARE THERAPY WITH A SAFETY LEAD-IN OF ENCORAFENIB AND CETUXIMAB PLUS CHEMOTHERAPY IN PARTICIPANTS WITH METASTATIC BRAF V600E-MUTANT COLORECTAL CANCER
Study Start DateDecember 20, 2020
Actual Primary Completion DateFebruary 28, 2025
Actual Study Completion Date1yr 5mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Safety Lead-in Cohort 1
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Drug: Encorafenib
75 mg capsules
Safety Lead-in Cohort 2
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Drug: Encorafenib
75 mg capsules
Phase 3 Arm A
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks
Drug: Encorafenib
75 mg capsules
Phase 3 Arm B
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120 minute IV infusion) every two weeks Oxaliplatin 85 mg/m2 (120-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Drug: Encorafenib
75 mg capsules
Phase 3 Arm C
Every two weeks: Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Every two weeks: Irinotecan 165 mg/m2 (90-minute IV infusion) Oxaliplatin 85 mg/m2 (120-minute IV infusion) Leucovorin 400 mg/m2 (120-minute IV infusion) 5-FU 2400 or 3200 mg/m2 continuous IV infusion over 46 48 hours Bevacizumab (optional; given per prescribing instructions) -OR- Oxaliplatin 130 mg/m2 (120-minute IV infusion) every 3 weeks Capecitabine 1000 mg/m2 oral tablet twice daily on Days 1-14 Bevacizumab (optional; given per prescribing instructions)
Drug: Oxaliplatin
Powder for solution for intravenous use 50 mg/vial, 100 mg/vial, or 200 mg/vial
Cohort 3 Arm D
Encorafenib 300 mg orally once daily Cetuximab 500 mg/m2 (120-minute IV infusion) every two weeks Irinotecan 180 mg/m2 (90-minute IV infusion) every two weeks Leucovorin 400 mg/m2 (120-minute IV infusion) every two weeks 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks
Drug: Encorafenib
75 mg capsules
Cohort 3 Arm E
Irinotecan 180 mg/m2 (90-minute IV infusion) every 2 weeks, Leucovorin 400 mg/m2 (120-minute IV infusion) every 2 weeks, 5-FU 400 mg/m2 IV bolus, then 5-FU 2400 mg/m2 continuous IV infusion over 46-48 hours every two weeks, Bevacizumab (optional; given per prescribing instructions)
Drug: Irinotecan
Solution for intravenous infusion 40 mg/vial, 100 mg/vial, or 300 mg/vial

Outcome Measures

Primary Outcome Measures
  1. SLI: Number of Participants With Dose Limiting Toxicity (DLTs)
    DLT: Any AE/lab value during first 28 days (D) of treatment that met at least 1 criteria: AE/lab value unrelated to underlying disease,PD,intercurrent illness,concomitant medications resulting in inability to tolerate atleast 75% of planned dose intensity of study drug,fatigue grade (G)3\>14 consecutive D, interstitial lung disease G\>=2,rash,hand foot skin reaction G3\>14 consecutive D or G4,diarrhea G3 \>=48 hours or G4,nausea/vomiting G3\>=48 hours or G4,mucositis G\>=3,total bilirubin G\>=3, aspartate aminotransferase/alanine aminotransferase G\>=3 in conjunction with total bilirubin G\>=2 or G3 \>7 consecutive D or G4,Serum creatinine G\>=3,absolute neutrophil count G4 \>7 consecutive D, \>=G3 febrile neutropenia,G3 platelet count decreased with signs of bleeding,platelet count G4,ECG QTcF prolonged \>=G3,G\>=3 uveitis \>21 consecutive D,G4 confirmed by ophthalmic examination,paresthesia/dysesthesias G\>=3,other G\>=3 hematologic/nonhematologic toxicity except lymphocyte count decreased G\>=3.
  2. Phase 3: Progression Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) for Arm B vs Arm C - FAS
    PFS was defined as the time from date of randomization to earliest documented disease progression (PD) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death due to any cause as assessed by BICR. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 millimeter (mm) for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \>12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
  3. Phase 3: Objective Response Rate (ORR) as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
    ORR was defined as the percentage of participants who achieved best overall response (BOR) of confirmed complete response (CR) or partial response (PR) according to RECIST v 1.1 as assessed by BICR. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
  4. Cohort 3: ORR as Assessed by BICR for Arm D vs Arm E - FAS
    ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
Secondary Outcome Measures
  1. SLI: Number of Participants With Adverse Events (AEs)
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. An Serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event. AEs included both SAEs and all non-SAEs.
  2. SLI: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention. AEs were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version (v) 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE. In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
  3. SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
    The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory abnormalities were graded according to NCI CTCAE version 4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death. Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  4. SLI: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
    The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased. Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening, and grade 5= death related to AE. Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  5. SLI: Number of Participants According to Categorization of Vital Signs Data
    The criteria for vital signs included: Systolic blood pressure (millimeters of mercury \[mmHg\]): value \&lt;= 90 mmHg and decrease from baseline \&gt;= 20 mmHg, and value \&gt;= 160 mmHg and increase from baseline \&gt;= 20 mmHg. Diastolic blood pressure (mmHg): value \&lt;= 50 mmHg and decrease from baseline \&gt;= 15 mmHg, and value \&gt;= 100 mmHg and increase from baseline \&gt;= 15 mmHg. Pulse rate (beats per minute \[bpm\]): value \&lt;= 50 bpm and decrease from baseline \&gt;= 15 bpm, and value \&gt;= 120 bpm and increase from baseline \&gt;= 15 bpm. Weight (kilograms \[kg\]): change \&gt;= 20 % decrease from baseline, and change \&gt;=10% increase from baseline. Temperature (degree Celsius): value \&lt;=36 degree Celsius, and value \&gt;=37.5 degree Celsius. Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
  6. SLI: Number of Participants According to Categorization of Electrocardiogram (ECGs) Findings
    ECG criteria included: ECG mean heart rate (beats per minute \[bpm\]): increase from baseline \&gt;25% and to a value \&gt;100 bpm; decrease from baseline \&gt;25% and to a value \&lt;50 bpm, PR interval not otherwise specified (milliseconds \[msec\]): new \&gt;280 msec, QRS interval not otherwise specified (msec): new \&gt;120 msec, QT Interval Corrected Using Fridericia&#039;s Formula (QTcF) not otherwise specified: new \&gt;450 msec; new \&gt;480 msec; new \&gt;500 msec; increase from baseline \&gt;30 msec and increase from baseline \&gt;60 msec. Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
  7. SLI: Number of Participants With Dose Modification of Any Study Intervention Due to AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention. Dose interruption: for encorafenib = 0 mg dose administered for \&gt;=1 days; for cetuximab, oxaliplatin, leucovorin, fluorouracil, irinotecan: \&gt;20 days between successive start dates with non-zero actual doses. Dose reduction: decrease in dose of at least 10%, from the protocol-planned dose and a decrease from the previous non-zero dose; for encorafenib to qualify as a dose reduction, it should have lasted for \&gt;=2 days. Dose modifications included both dose interruptions and reduction.
  8. SLI: Number of Participants With Dose Discontinuation of Any Study Intervention Due to AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether or not considered related to study intervention. Number of participants with dose discontinuation due to AEs were reported in this outcome measure.
  9. SLI: ORR as Assessed by Investigator According to Line of Therapy - FAS
    ORR: percentage of participants who achieved BOR of confirmed CR/PR per RECIST v1.1 as assessed by response reported by investigator on eCRF. CR: complete disappearance of all target lesions (with exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis \&lt;10 mm. PR: \&gt;=30% decrease under baseline of sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Percentage of participants with ORR for first line (no prior treatment) and second line (participant received prior treatment viz. advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of last therapy dose) is presented.
  10. SLI: Duration of Response (DOR) as Assessed by Investigator According to Line of Therapy - FAS
    DOR: time from date of first radiographic evidence of response (CR/PR) to earliest documented PD per RECIST v1.1 as assessed by response reported by investigator on eCRF, or death by any cause. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis \&lt;10 mm. PR: \&gt;=30% decrease under baseline of sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. DOR for first line and second line is presented. Analysis performed by Kaplan Meier method.
  11. SLI: PFS as Assessed by Investigator According to Line of Therapy - FAS
    PFS: time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by response reported by investigator on eCRF. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \&gt;12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Participants with PFS for first line and second line were presented. Analysis performed using Kaplan Meier method.
  12. SLI: Time to Response (TTR) as Assessed by Investigator According to Line of Therapy - FAS
    TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by response reported by investigator on eCRF. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions. In this outcome measure, TTR for first line (no prior treatment) and second line (participant received a prior treatment defined as advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of the last dose of therapy) were reported.
  13. SLI: Overall Survival (OS) According to Line of Therapy - FAS
    OS was defined as the time from the date of first dose to death due to any cause. If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact. In this outcome measure, OS for first line (no prior treatment) and second line (participant received a prior treatment defined as advanced/metastatic or locoregional disease or maintenance or if neoadjuvant/adjuvant with a disease recurrence occurred during or within 6 months of the last dose of therapy) was presented. Analysis was performed using Kaplan Meier method.
  14. SLI: Maximum Plasma Concentration (Cmax) of Encorafenib and Its Metabolite LHY746
    Cmax was observed directly from data. LHY746 is a metabolite of Encorafenib.
  15. SLI: Area Under the Concentration Time Profile From Time Zero to 6 Hours (AUC6) for Encorafenib and Its Metabolite LHY746
    The AUC was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. LHY746 is a metabolite of Encorafenib.
  16. SLI: Area Under the Concentration-time Profile From Time Zero to the Time Tau (AUCtau) of Encorafenib and Its Metabolite LHY746
    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval. tau = 24 hrs for QD dosing of encorafenib. LHY746 is a metabolite of encorafenib. AUCtau can be calculated directly from the data using 24 hrs (tau) sample or can be approximately calculated by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
  17. SLI: Time to Maximum Plasma Concentration (Tmax) of Encorafenib and Its Metabolite LHY746
    Tmax: time (hours) to Cmax. LHY746 is a metabolite of Encorafenib.
  18. SLI: Apparent Total Clearance (CL/F) of Encorafenib
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as Dose/AUCinf where dose is the dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is last plasma concentration from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
  19. SLI, Cohort 1: Cmax of Irinotecan and Its Metabolite SN-38
    Cmax was observed directly from data. SN-38 is a metabolite of Irinotecan.
  20. SLI, Cohort 1: AUClast of Irinotecan and Its Metabolite SN-38
    AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration. AUClast was calculated using linear/log trapezoidal method. SN-38 is a metabolite of Irinotecan.
  21. SLI, Cohort 1: Apparent Terminal Elimination Half-Life (t1/2) of Irinotecan and Its Metabolite SN-38
    t1/2 was the time measured for the drug concentration to decrease by one half. t1/2 was determined by Loge (2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. SN-38 is a metabolite of Irinotecan.
  22. SLI, Cohort 1: CL/F of Irinotecan
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
  23. SLI, Cohort 2: Cmax of Oxaliplatin
    Cmax was observed directly from data. Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
  24. SLI, Cohort 2: AUClast of Oxaliplatin
    AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration. AUClast was calculated using linear/log trapezoidal method. Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate.
  25. SLI, Cohort 2: CL/F of Oxaliplatin
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. Oxaliplatin consisted of platinum of plasma and platinum in plasma-ultrafiltrate. The clearance of platinum-ultrafiltrate has been presented in this outcome measure.
  26. SLI, Cohort 1: Ratio of AUCinf on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
    AUCinf was calculated as AUClast + (Clast\*/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve. The ratio between geometric least square (LS) mean (within Cohort 1) for AUCinf on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for AUCinf on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as &quot;Number&quot;.
  27. SLI, Cohort 1: Ratio of AUClast on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
    AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration. AUClast was calculated using linear/log trapezoidal method. The ratio between geometric LS mean (within Cohort 1) for AUClast on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for AUClast on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as &quot;Number&quot;.
  28. SLI, Cohort 1: Ratio of Cmax on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Irinotecan and Its Metabolite SN-38
    Cmax was observed directly from data. The ratio between geometric LS mean (within Cohort 1) for Cmax on Cycle 1 Day 15 and geometric LS mean (within Cohort 1) for Cmax on Cycle 1 Day 1 for irinotecan and its metabolite SN-38 has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as &quot;Number&quot;.
  29. SLI, Cohort 2: Ratio of AUClast on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
    AUClast was defined as area under the plasma concentration time curve from time zero to the last measurable concentration. AUClast was calculated using linear/log trapezoidal method. Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate. The ratio between geometric LS mean (within Cohort 2) for AUClast on Cycle 1 Day 15 and geometric LS mean (within Cohort 2) for AUClast on Cycle 1 Day 1 for Oxaliplatin has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as &quot;Number&quot;.
  30. SLI, Cohort 2: Ratio of Cmax on Cycle 1 Day 15 as Compared to Cycle 1 Day 1 for Oxaliplatin
    Cmax was observed directly from data. Oxaliplatin was evaluated as total platinum in plasma and platinum in plasma ultrafiltrate. The ratio between geometric LS mean (within Cohort 2) for Cmax on Cycle 1 Day 15 and geometric LS mean (within Cohort 2) for Cmax on Cycle 1 Day 1 for Oxaliplatin has been presented in this outcome measure, which explains the data reported for this outcome measure using measure type as &quot;Number&quot;.
  31. Phase 3: OS for Arm B vs Arm C - FAS
    OS was defined as the time from the date of first dose to death due to any cause. If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact. Analysis was performed using Kaplan Meier method.
  32. Phase 3: ORR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
    ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
  33. Phase 3: ORR as Assessed by BICR - FAS
    ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 as assessed by BICR. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
  34. Phase 3: DOR as Assessed by BICR for Arm B Versus Arm C - FAS ORR Subset
    DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 as assessed by BICR, or death due to any cause. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Analysis was performed using Kaplan Meier method.
  35. Phase 3: DOR by Derived Investigator Assessment for Arm B Versus Arm C - FAS ORR Subset
    DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 by derived investigator assessment, or death due to any cause. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Analysis was performed using Kaplan Meier method.
  36. Phase 3: PFS as Assessed by BICR - FAS
    PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \&gt;12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
  37. Phase 3: OS - FAS
    OS was defined as the time from the date of first dose to death due to any cause. If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact. Analysis was performed using Kaplan Meier method.
  38. Phase 3: PFS by Derived Investigator Assessment - FAS
    PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \&gt;12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
  39. Phase 3: TTR as Assessed by BICR for Arm B vs Arm C - FAS ORR Subset
    TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
  40. Phase 3: TTR by Derived Investigator Assessment for Arm B vs Arm C - FAS ORR Subset
    TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 by derived investigator assessment. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
  41. Phase 3: Progression After Next Line of Treatment (PFS2) - FAS
    PFS2 was defined as the time from the date of randomization to the date of discontinuation of next-line treatment after first objective PD by investigator assessment, to second objective disease progression (PD2), or death from any cause, whichever occurred first. PD2: was progressive disease after the start of subsequent anticancer therapy based on investigator assessment. PFS2 was censored at start date of next-line anticancer treatment (NTX) if PD date \&gt; NTX start date and there was no death, at last contact date if withdrawal of consent date \&gt;= date of randomization or end of study or if participant lost to follow-up or if no prior conditions are met or PD and no NTX and there was no death.
  42. Phase 3: Number of Participants With AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event. AEs included both SAEs and all non-SAEs.
  43. Phase 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE. In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
  44. Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
    The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death. Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  45. Phase 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
    The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased. Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE. Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  46. Phase 3: Number of Participants According to Categorization of Vital Signs Data
    The criteria for vital signs included: Systolic blood pressure (mmHg): value \&lt;= 90 mmHg and decrease from baseline \&gt;= 20 mmHg, and value \&gt;= 160 mmHg and increase from baseline \&gt;= 20 mmHg. Diastolic blood pressure (mmHg): value \&lt;= 50 mmHg and decrease from baseline \&gt;= 15 mmHg, and value \&gt;= 100 mmHg and increase from baseline \&gt;= 15 mmHg. Pulse rate (bpm): value \&lt;= 50 bpm and decrease from baseline \&gt;= 15 bpm, and value \&gt;= 120 bpm and increase from baseline \&gt;= 15 bpm. Weight (kg): change \&gt;= 20 % decrease from baseline, and change \&gt;=10% increase from baseline. Temperature (degree Celsius): value \&lt;=36 degree Celsius, and value \&gt;=37.5 degree Celsius. Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
  47. Phase 3: Number of Participants According to Categorization of ECGs Findings
    ECG criteria included: ECG mean heart rate (bpm): increase from baseline \&gt;25% and to a value \&gt;100 bpm; decrease from baseline \&gt;25% and to a value \&lt;50 bpm, PR interval not otherwise specified (msec): new \&gt;280 msec, QRS interval not otherwise specified (msec): new \&gt;120 msec, QTcF not otherwise specified: new \&gt;450 msec; new \&gt;480 msec; new \&gt;500 msec; increase from baseline \&gt;30 msec and increase from baseline \&gt;60 msec. Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
  48. Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients - 30 Item Core Questionnaire (EORTC QLQC30) Global Health Status/Quality of Life Scores (QoL) at Baseline and Week 72
    EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These included five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Global health status/QoL scale ranged from 0 to 100; the higher score represents better level of functioning. In this outcome measure, global health status/QoL scores are presented.
  49. Phase 3: EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) Visual Analogue Score (VAS) at Baseline and Week 72
    EQ-5D-5L is a standardized measure of health status. The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS. For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
  50. Phase 3: Number of Participants According to Response to Patient Global Impression of Severity (PGIS) Assessment at Baseline and at Week 30
    PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
  51. Phase 3: Number of Participants According to Response to Patient Global Impression of Change (PGIC) Assessment at Week 30
    The PGIC is a single-item scale where participants rated the overall change in colorectal cancer since participant started taking the study medication as follows: much better, a little better, no change, a little worse, and much worse.
  52. Phase 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
    Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
  53. Phase 3: Cmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
    Cmax was observed directly from data. LHY746 is a metabolite of Encorafenib.
  54. Phase 3: AUC6 of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
    The AUC was estimated from time 0 to 6 hours post dose. AUC6 was computed using the Linear/Log trapezoidal method. LHY746 is a metabolite of Encorafenib.
  55. Phase 3: AUCtau of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
    AUCtau was area under the concentration-time profile from time zero to time tau, the dosing interval. tau = 24 hrs for QD dosing of encorafenib. LHY746 is a metabolite of encorafenib.
  56. Phase 3: Tmax of Encorafenib and Its Metabolite LHY746 in Mainland China Participants
    Tmax: time (hours) to Cmax. LHY746 is a metabolite of Encorafenib.
  57. Phase 3: CL/F of Encorafenib in Mainland China Participants
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F was calculated as dose administered divided by area under the concentration curve from time 0 extrapolated to infinite time (AUCinf). AUCinf was calculated as AUClast + (Clast\*/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration-time curve.
  58. Phase 3: Number of Participants Classified According to Microsatellite Instability (MSI) Status as Determined by Retrospective Central Testing of Baseline Tumor Tissue
    MSI status was classified as follows; microsatellite instability-high (MSI-H): included participants with no negative test results and at least one positive test result, microsatellite stable (MSS): included participants with at least one negative test result and MSI-unknown: included participants with intermediate test results or not analyzed for MSI. The number of participants as per their MSI status (MSI-H, MSS, and MSI-unknown) have been reported in this outcome measure.
  59. Phase 3: Number of Participants According to Circulating Tumor Deoxyribonucleic Acid (ctDNA) Status
    ctDNA status was classified as follows; detected: overall variant allele frequency (VAF) was greater than zero, not detected: overall VAF equalled zero, and not evaluable: overall VAF could not be calculated. The VAF was defined as percentage of deoxyribonucleic acid (DNA) reads at a specific position that show a genetic variant instead of the normal (reference) sequence. The number of participants as per their ctDNA status (detected, not detected and not evaluable) have been reported in this outcome measure.
  60. Phase 3: Number of Participants According to B-Raf Serine/Threonine-Protein Kinase (BRAF) Valine 600 (V600) Status From ctDNA
    BRAF V600 status from ctDNA was classified as follows; measurable: participants with detectable ctDNA had measurable BRAF V600 tumor biomarker alterations and not measurable: participants with detectable ctDNA did not have measurable BRAF V600 biomarker alterations or overall ctDNA was not detectable. The number of participants as per their BRAF V600 status from ctDNA (measurable and not measurable) have been reported in this outcome measure. In this outcome measure, data is presented for participants outside China and Mainland China participants.
  61. Cohort 3: PFS as Assessed by BICR - FAS
    PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause as assessed by BICR. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \&gt;12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
  62. Cohort 3: ORR by Derived Investigator Assessment - FAS
    ORR was defined as the percentage of participants who achieved BOR of confirmed CR or PR according to RECIST v 1.1 by derived investigator assessment. CR: complete disappearance of all target lesions (with the exception of nodal disease) and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;=30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion.
  63. Cohort 3: DOR as Assessed by BICR - FAS
    DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 as assessed by BICR, or death due to any cause. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Analysis was performed using Kaplan Meier method.
  64. Cohort 3: DOR by Derived Investigator Assessment - FAS
    DOR was defined as the time from the date of first radiographic evidence of response (CR or PR) to the earliest documented PD per RECIST v1.1 by derived investigator assessment, or death due to any cause. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Analysis was performed using Kaplan Meier method.
  65. Cohort 3: PFS by Derived Investigator Assessment - FAS
    PFS was defined as the time from date of randomization to earliest documented PD per RECIST version 1.1 or death due to any cause by derived investigator assessment. PD: 20% increase in sum of diameters of target measurable lesions above smallest sum observed, with minimum absolute increase of 5 mm for target disease or unequivocal progression of pre-existing lesions for non-target disease or any new lesion. Censoring details: no adequate baseline assessment, including no disease at baseline: participants were censored to randomization date; no PD, lost to follow-up, withdrawal of consent, PD or death \&gt;12 (or 16) weeks after the last adequate tumor assessment, and start of new anticancer treatment: participants were censored to last adequate tumor assessment documenting no PD prior to new anticancer therapy, or missed assessments. Analysis was performed using Kaplan Meier method.
  66. Cohort 3: OS - FAS
    OS was defined as the time from the date of first dose to death due to any cause. If a participant was not known to have died at the time of the cutoff for analysis, then OS was censored at the date of last contact. Analysis was performed using Kaplan Meier method.
  67. Cohort 3: TTR as Assessed by BICR - FAS
    TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 as assessed by BICR. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
  68. Cohort 3: TTR by Derived Investigator Assessment - FAS
    TTR was defined as the time from the date of first dose to first radiographic evidence of response (CR or PR) per RECIST v1.1 by derived investigator assessment. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \&lt;10 mm. PR: \&gt;= 30% decrease under baseline of the sum of diameters of all target measurable lesions.
  69. Cohort 3: Number of Participants With AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. SAE was defined as any untoward medical occurrence that, at any dose, met one or more of the following criteria - resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or other important medical event. AEs included both SAEs and all non-SAEs.
  70. Cohort 3: Number of Participants With Grade 3 or 4 AEs and Grade 5 AEs
    An AE was any untoward medical occurrence in clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. AEs were graded according to NCI-CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE. In this outcome measure, number of participants with grade 3 or 4 AEs and grade 5 AEs were reported.
  71. Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Hematology and Coagulation Parameters
    The following hematology and coagulation parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening event due to AE, and grade 5= death. Only those hematology and coagulation parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  72. Cohort 3: Number of Participants With Shift From Grade <=2 at Baseline to Grade >=3 Post-Baseline in Chemistry Parameters
    The following chemistry parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and lipase increased. Laboratory abnormalities were graded according to NCI CTCAE v4.03 where grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening and grade 5= death related to AE. Only those chemistry parameters in which at least 1 participant in any of the reporting arm had any shift from grade \&lt;=2 at baseline to grade \&gt;=3 post-baseline are reported in this outcome measure.
  73. Cohort 3: Number of Participants According to Categorization of Vital Signs Data
    The criteria for vital signs included: Systolic blood pressure (mmHg): value \&lt;= 90 mmHg and decrease from baseline \&gt;= 20 mmHg, and value \&gt;= 160 mmHg and increase from baseline \&gt;= 20 mmHg. Diastolic blood pressure (mmHg): value \&lt;= 50 mmHg and decrease from baseline \&gt;= 15 mmHg, and value \&gt;= 100 mmHg and increase from baseline \&gt;= 15 mmHg. Pulse rate (bpm): value \&lt;= 50 bpm and decrease from baseline \&gt;= 15 bpm, and value \&gt;= 120 bpm and increase from baseline \&gt;= 15 bpm. Weight (kg): change \&gt;= 20 % decrease from baseline, and change \&gt;=10% increase from baseline. Temperature (degree Celsius): value \&lt;=36 degree Celsius, and value \&gt;=37.5 degree Celsius. Only those criteria in which at least 1 participant in any of the reporting arm had any vital signs data are reported in this outcome measure.
  74. Cohort 3: Number of Participants According to Categorization of ECGs Findings
    ECG criteria included: ECG mean heart rate (bpm): increase from baseline \&gt;25% and to a value \&gt;100 bpm; decrease from baseline \&gt;25% and to a value \&lt;50 bpm, PR interval not otherwise specified (msec): new \&gt;280 msec, QRS interval not otherwise specified (msec): new \&gt;120 msec, QTcF not otherwise specified: new \&gt;450 msec; new \&gt;480 msec; new \&gt;500 msec; increase from baseline \&gt;30 msec and increase from baseline \&gt;60 msec. Only those criteria in which at least 1 participant in any of the reporting arm had any ECG findings are reported in this outcome measure.
  75. Cohort 3: EORTC QLQC30 Global Health Status/QoL
    EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures. These included five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale. Global health status/QoL scale ranged from 0 to 100; the higher score represents better level of functioning.
  76. Cohort 3: EQ-5D-5L VAS
    EQ-5D-5L is a standardized measure of health status. The EQ-5D-5L consisted of EQ-5D-5L descriptive system and the EQ VAS. For EQ VAS participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
  77. Cohort 3: Number of Participants According to Response to PGIS Assessment
    PGIS is a single-item scale where participants rated the severity of colorectal cancer as follows: none, mild, moderate, severe and very severe.
  78. Cohort 3: Number of Participants According to Response to PGIC Assessment
    The PGIC is a single-item scale where participants rated the overall change in colorectal cancer since participant started taking the study medication as follows: much better, a little better, no change, a little worse, and much worse.
  79. Cohort 3: Trough Plasma Concentration of Encorafenib and Its Metabolite LHY746
    Trough plasma concentration of encorafenib and its metabolite LHY746 was measured in this outcome measure.
  80. Cohort 3: Number of Participants Classified According to MSI Status as Determined by Retrospective Central Testing
    MSI status was classified as follows; MSI-H: included participants with no negative test results and at least one positive test result, MSS: included participants with at least one negative test result and MSI-unknown: included participants with intermediate test results or not analyzed for MSI. The number of participants as per their MSI status (MSI-H, MSS, and MSI-unknown) have been reported in this outcome measure.
  81. Cohort 3: Number of Participants According to ctDNA Status
    ctDNA status was classified as follows; detected: overall variant allele frequency (VAF) was greater than zero, not detected: overall VAF equalled zero, and not evaluable: overall VAF could not be calculated. The VAF was defined as percentage of deoxyribonucleic acid (DNA) reads at a specific position that show a genetic variant instead of the normal (reference) sequence. The number of participants as per their ctDNA status (detected, not detected and not evaluable) have been reported in this outcome measure.
  82. Cohort 3: Number of Participants According to BRAF V600 Status From ctDNA
    BRAF V600 status from ctDNA was classified as follows; measurable: participants with detectable ctDNA had measurable BRAF V600 tumor biomarker alterations and not measurable: participants with detectable ctDNA did not have measurable BRAF V600 biomarker alterations or overall ctDNA was not detectable. The number of participants as per their BRAF V600 status from ctDNA (measurable and not measurable) have been reported in this outcome measure.

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Safety Lead-In = Male/female ≥ 18 years old
Phase 3 and Cohort 3: Male/female ≥ 16 years old (where permitted locally)
Histologically or cytologically confirmed Stage IV CRC that contains BRAF V600E mutation
Prior systemic treatment in metastatic setting: 0-1 regimens for Safety Lead In; none for Phase 3 and Cohort 3. (Note: Prior adjuvant or neoadjuvant therapy considered metastatic treatment if relapse/metastasis \< 6 month from end of adj/neoadjuvant treatment )
Measurable disease (Phase 3 and Cohort 3)/ Measurable or evaluable disease (Safety Lead-in)
ECOG PS 0-1
Adequate organ function
Exclusion Criteria
Tumors that are locally confirmed or unknown MSI-H or dMMR unless participant is ineligible to receive immune checkpoint inhibitors due to a pre-existing medical condition
Active bacterial or viral infections in 2 weeks prior to starting dosing
Symptomatic brain metastases

Contacts and Locations

Sponsors and CollaboratorsPfizer
Locations
Mayo Clinic Hospital | Phoenix Arizona, United States, 85054Mayo Clinic in Arizona - Scottsdale | Scottsdale Arizona, United States, 85259Keck Hospital of USC | Los Angeles California, United States, 90033LAC & USC Medical Center | Los Angeles California, United States, 90033USC / Norris Comprehensive Cancer Center | Los Angeles California, United States, 90033USC/Norris Comprehensive Cancer Center/Investigational Drug Services | Los Angeles California, United States, 90033USC/Norris Comprehensive Cancer Center | Los Angeles California, United States, 90033Keck Hospital of USC Pasadena | Pasadena California, United States, 91105Mount Sinai Comprehensive Cancer Center, Aventura | Aventura Florida, United States, 33180Mount Sinai Comprehensive Cancer Center | Miami Beach Florida, United States, 33140Mount Sinai Medical Center | Miami Beach Florida, United States, 33140BRCR Global | Plantation Florida, United States, 33322BRCR Medical Center Inc. | Plantation Florida, United States, 33322UChicago Medicine - River East | Chicago Illinois, United States, 60611University of Chicago Medical Center | Chicago Illinois, United States, 60637UChicago Medicine at Ingalls - Flossmoor | Flossmoor Illinois, United States, 60422UChicago Medicine Ingalls Memorial | Harvey Illinois, United States, 60426University of Chicago Comprehensive Cancer Center at Silver Cross Hospital | New Lenox Illinois, United States, 60451The University of Chicago Medicine Center for Advanced Care Orland Park | Orland Park Illinois, United States, 60462UChicago Medicine at Ingalls - Tinley Park | Tinley Park Illinois, United States, 60477Ochsner Clinic Foundation | New Orleans Louisiana, United States, 70121Mayo Clinic Rochester | Rochester Minnesota, United States, 55905Siteman Cancer Center - St Peters | City of Saint Peters Missouri, United States, 63376Siteman Cancer Center - West County | Creve Coeur Missouri, United States, 63141Siteman Cancer Center - North County | Florissant Missouri, United States, 63031Barnes- Jewish Hospital | St Louis Missouri, United States, 63110Washington University School of Medicine | St Louis Missouri, United States, 63110Siteman Cancer Center - South County | St Louis Missouri, United States, 63129Oncology Hematology West PC dba Nebraska Cancer Specialists | Omaha Nebraska, United States, 68114Oncology Hematology West PC dba Nebraska Cancer Specialists | Omaha Nebraska, United States, 68124Oncology Hematology West PC dba Nebraska Cancer Specialists | Omaha Nebraska, United States, 68130Oncology Hematology West PC dba Nebraska Cancer Specialists | Papillion Nebraska, United States, 68046Memorial Sloan Kettering Cancer Center - Basking Ridge | Basking Ridge New Jersey, United States, 07920Summit Medical Group | Berkeley Heights New Jersey, United States, 07922Summit Medical Group | Florham Park New Jersey, United States, 07932Memorial Sloan Kettering Cancer Center- Monmouth | Middletown New Jersey, United States, 07748Memorial Sloan Kettering Cancer Center- Bergen | Montvale New Jersey, United States, 07645Memorial Sloan Kettering Cancer Center Commack | Commack New York, United States, 11725Memorial Sloan Kettering Cancer Center - Westchester | Harrison New York, United States, 10604Memorial Sloan Kettering Cancer Center | New York New York, United States, 10022Memorial Sloan Kettering Cancer Center - Main Campus | New York New York, United States, 10065Memorial Sloan Kettering Cancer Center- Nassau | Uniondale New York, United States, 11553Cleveland Clinic Taussig Cancer Center Investigational Pharmacy | Cleveland Ohio, United States, 44195Cleveland Clinic | Cleveland Ohio, United States, 44195The Ohio State University James Cancer Hospital and Solove Research Institute | Columbus Ohio, United States, 43210The Ohio State University Wexner Medical Center Investigational Drug Services | Columbus Ohio, United States, 43210Stefanie Spielman Comprehensive Breast Cancer | Columbus Ohio, United States, 43212Martha Morehouse Medical Plaza | Columbus Ohio, United States, 43221University of Oklahoma Health Sciences Center, OU Health Stephenson Cancer Center | Oklahoma City Oklahoma, United States, 73104Providence Cancer Institute Franz Clinic | Portland Oregon, United States, 97213Providence Portland Medical Center | Portland Oregon, United States, 97213Providence Onc and Heme Care Clinic - Westside | Portland Oregon, United States, 97225Providence St Vincent Medical Center | Portland Oregon, United States, 97225UPMC Hillman Cancer Center | Pittsburgh Pennsylvania, United States, 15232The West Clinic. PLLC. dba West Cancer Center | Germantown Tennessee, United States, 38138Henry-Joyce Cancer Clinic | Nashville Tennessee, United States, 37232Vanderbilt-Ingram Cancer Center | Nashville Tennessee, United States, 37232The University of Texas MD Anderson Cancer Center | Houston Texas, United States, 77030Virginia Commonwealth University | Richmond Virginia, United States, 23219Seattle Cancer Care Alliance | Seattle Washington, United States, 98109University of Washington Medical Center | Seattle Washington, United States, 98195University of Wisconsin Clinical Science Center | Madison Wisconsin, United States, 53792Centro Medico San Roque | San Miguel de Tucumán Tucumán Province, Argentina, 4000Instituto Médico Especializado Alexander Fleming | Buenos Aires , Argentina, 1426Clinica Universitaria Reina Fabiola | Córdoba , Argentina, X5004FHPHospital Privado Centro Médico de Córdoba | Córdoba , Argentina, X5016KEHChris O'Brien Lifehouse | Camperdown New South Wales, Australia, 2050Liverpool Hospital | Liverpool New South Wales, Australia, 2170GenesisCare - North Shore | St Leonards New South Wales, Australia, 2065GenesisCare North Shore | St Leonards New South Wales, Australia, 2065Royal Brisbane and Women's Hospital | Herston Queensland, Australia, 4029Princess Alexandra Hospital | Woolloongabba Queensland, Australia, 4102Central Adelaide Local Health Network Incorporated | Adelaide South Australia, Australia, 5000The Queen Elizabeth Hospital | Adelaide South Australia, Australia, 5011Monash Health | Clayton Victoria, Australia, 3168Austin Health | Heidelberg Victoria, Australia, 3084Peter MacCallum Cancer Centre | Melbourne Victoria, Australia, 3000Alfred Health | Melbourne Victoria, Australia, 3004Université Libre de Bruxelles - Hôpital Erasme | Brussels Bruxelles-capitale, Région de, Belgium, 1070Cliniques universitaires Saint-Luc | Brussels Bruxelles-capitale, Région de, Belgium, 1200Grand Hôpital de Charleroi | Charleroi Hainaut, Belgium, 6060AZ Groeninge Campus Kennedylaan | Kortrijk West-vlaanderen, Belgium, 8500ZNA Middelheim | Antwerp , Belgium, 2020UZ Leuven | Leuven , Belgium, 3000Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman | Liège , Belgium, 4000ZAS Augustinus | Wilrijk , Belgium, 2610Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA | Rio de Janeiro Rio de Janeiro, Brazil, 20230-130Hospital de Clinicas de Porto Alegre | Porto Alegre Rio Grande do Sul, Brazil, 90035-903Reichow - Centro de Ensino e Pesquisa | Blumenau Santa Catarina, Brazil, 89010-340Clínica de Neoplasias Litoral | Itajaí Santa Catarina, Brazil, 88301-220Fundação Pio XII - Hospital de Câncer de Barretos | Barretos São Paulo, Brazil, 14.780-070Fundação Pio XII - Hospital de Câncer de Barretos | Barretos São Paulo, Brazil, 14784400CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia - Faculdade de Medicina do ABC | Santo André São Paulo, Brazil, 09060-650FUNDAÇÃO DO ABC - Faculdade de Medicina do ABC - Centro de Estudos e Pesquisas de Hematologia e Onco | Santo André São Paulo, Brazil, 09060-870Fundação Faculdade Regional de Medicina de São José do Rio Preto | São José do Rio Preto São Paulo, Brazil, 15090000MHAT Uni Hospital OOD | Panagyurishte Pazardzhik, Bulgaria, 4500MHAT "Dr. Tota Venkova" AD | Gabrovo , Bulgaria, 5300MHAT Central Onco Hospital OOD | Plovdiv , Bulgaria, 4000Complex Oncology Center - Plovdiv EOOD | Plovdiv , Bulgaria, 4004Medical Center Nadezhda Clinical EOOD | Sofia , Bulgaria, 1303Acibadem City Clinic MHAT Tokuda | Sofia , Bulgaria, 1407University Multiprofile Hospital for Active Treatment Sofiamed | Sofia , Bulgaria, 1750Alberta Health Services - Cancer Care, Tom Baker Cancer Centre | Calgary Alberta, Canada, T2N 4N2Arthur J.E. Child Comprehensive Cancer Centre | Calgary Alberta, Canada, T3N 4N1Cross Cancer Institute | Edmonton Alberta, Canada, T6G 1Z2Alberta Health Services and The Governors of The University of Alberta | Edmonton Alberta, Canada, T6G 2C8London Regional Cancer Program, London Health Sciences Centre | London Ontario, Canada, N6A 5W9Sunnybrook Health Sciences Centre | Toronto Ontario, Canada, M4N 3M5Jewish General Hospital | Montreal Quebec, Canada, H3T 1E2Cancer Hospital Chinese Academy of Medical Science | Beijing Beijing Municipality, China, 100021Peking University First Hospital | Beijing Beijing Municipality, China, 100034Beijing Cancer hospital | Beijing Beijing Municipality, China, 100142Beijing Hospital | Beijing Beijing Municipality, China, 100730Chongqing University Cancer Hospital | Chongqing Chongqing Municipality, China, 400030Fujian Medical University Union Hospital | Fuzhou Fujian, China, 350001The Sixth Affiliated Hospital of Sun Yat-sen University | Guangzhou Guangdong, China, 510655Affiliated Tumor Hospital of Guangxi Medical University | Nanning Guangxi, China, 530200Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology | Wuhan Hubei, China, 430030The Second Xiangya Hospital of Central South University | Changsha Hunan, China, 410011The Third Xiangya Hospital of Central South University | Changsha Hunan, China, 410013Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School | Nanjing Jiangsu, China, 210008Shengjing Hospital Of China Medical University | Shenyang Liaoning, China, 110022Shandong province cancer hospital | Jinan Shandong, China, 250117Shanghai General Hospital | Shanghai Shanghai Municipality, China, 200080Ruijin Hospital Shanghai Jiaotong University School of Medicine | Shanghai Shanghai Municipality, China, 201800Sichuan Province Cancer Hospital | Chengdu Sichuan, China, 610041Yunnan Cancer Hospital(The Third Affiliated Hospital of Kunming Medical University) | Kunming Yunnan, China, 650118The second Affiliated Hospital of College of Medicine, Zhejiang University | Hangzhou Zhejiang, China, 310000Fudan University Shanghai Cancer Center | Shanghai , China, 201321Tianjin Union Medical Center | Tianjin , China, 300000Fakultní nemocnice Brno Bohunice | Brno Brno-město, Czechia, 625 00Fakultni nemocnice Hradec Kralove | Hradec Králové Hradec Králové, Czechia, 500 05Fakultni Thomayerova nemocnice | Prague Praha 4, Czechia, 14059Fakultni nemocnice Olomouc | Olomouc , Czechia, 779 00Fakultni nemocnice Bulovka | Prague , Czechia, 180 81Aalborg Universitetshospital, Syd | Aalborg North Denmark, Denmark, 9000Vejle Hospital-Sygehus Lillebaelt | Vejle Region Syddanmark, Denmark, 7100Vejle Sygehus | Vejle Region Syddanmark, Denmark, 7100Rigshospitalet | Copenhagen , Denmark, 2100Herlev and Gentofte Hospital | Herlev , Denmark, 2730Odense University Hospital | Odense C , Denmark, 5000Turku University Hospital | Turku Southwest Finland, Finland, 20520Docrates Syöpäsairaala | Helsinki Uusimaa, Finland, 00180Helsinki University Central Hospital | Helsinki Uusimaa, Finland, 00290Oulu University Hospital | Oulu , Finland, 90220Satakunnan Keskussairaala | Pori , Finland, 28500Tampereen yliopistollinen sairaala | Tampere , Finland, 33520Tampereen yliopistollinen sairaala | Tampere , Finland, 33521Turku University Hospital | Turku , Finland, 20520Muenchen Klinik Neuperlach, Klinik fuer Haematologie und Onkologie | Munich Bavaria, Germany, 81737Institut für Klinisch Onkologische Forschung | Frankfurt am Main Hesse, Germany, 60488Medizinische Hochschule Hannover | Hanover Lower Saxony, Germany, 30625Universitätsklinikum Leipzig | Leipzig Saxony, Germany, 04103Onkologische Schwerpunktpraxis Kurfuerstendamm | Berlin , Germany, 10707HELIOS Klinikum Berlin Buch GmbH | Berlin , Germany, 13125Radiologie Berlin | Charlottenburg , Germany, 10719Technische Universität Dresden, Medizinische Fakultät Carl Gustav Carus | Dresden , Germany, 01307Universitätsklinikum Carl Gustav Carus Dresden | Dresden , Germany, 01307Facharztzentrum Eppendorf | Hamburg , Germany, 20249ZytoService Deutschland GmbH, Standort-Hamburg-Jenfeld | Hamburg , Germany, 22045Radiologie im Israelitischen Krankenhaus | Hamburg , Germany, 22297Tata Memorial Hospital | Mumbai Maharashtra, India, 400012Deenanath Mangeshkar Hospital & Research Centre | Pune Maharashtra, India, 411 004Sahyadri Speciality Hospital | Pune Maharashtra, India, 411 004Bhakti Vedanta Hospital and Research Institute | Thane Maharashtra, India, 401107Rajiv Gandhi Cancer Institute And Research Centre | New Delhi National Capital Territory of Delhi, India, 110085Sawai Man Singh Medical College Hospital (SMS Hospital) | Jaipur Rajasthan, India, 302004Azienda Ospedaliera Universitaria di Cagliari - Presidio Policlinico Universitario "D.Casula" | Monserrato (CA) Cagliari, Italy, 09042IRCCS Casa Sollievo della Sofferenza | San Giovanni Rotondo Foggia, Italy, 71013ASST Grande Ospedale Metropolitano Niguarda | Milan Milano, Italy, 20162Fondazione del Piemonte per l'Oncologia - Istituto di Candiolo IRCCS | Candiolo Torino, Italy, 10060Azienda Ospedaliero Universitaria San Luigi Gonzaga | Orbassano Torino, Italy, 10043Fondazione Poliambulanza Istituto Ospedaliero | Brescia , Italy, 25124Istituto Europeo di Oncologia IRCCS | Milan , Italy, 20141Azienda Ospedaliera Universitaria dell'Università "Luigi Vanvitelli" di Napoli | Naples , Italy, 80131IRCCS Istituto Oncologico Veneto (IOV) | Padova , Italy, 35128Azienda USL - IRCCS di Reggio Emilia - Arcispedale Santa Maria Nuova | Reggio Emilia , Italy, 42123Chiba cancer center | Chiba Chiba, Japan, 260-8717National Cancer Center Hospital East | Kashiwa Chiba, Japan, 277-8577Hokkaido University Hospital | Sapporo Hokkaido, Japan, 060-8648Kanazawa University Hospital | Kanazawa Ishikawa-ken, Japan, 920-8641St. Marianna University Hospital | Kawasaki Kanagawa, Japan, 216-8511Kanagawa cancer center | Yokohama Kanagawa, Japan, 2418515Aichi Cancer Center Hospital | Nagoya Nagoya, Aichi, Japan, 464-8681Osaka Prefectural Hospital Organization Osaka International Cancer Institute | Osaka Osaka, Japan, 5418567Kindai University Hospital | Sayama Osaka, Japan, 589-8511Osaka University Hospital | Suita Osaka, Japan, 565-0871Osaka Medical and Pharmaceutical University Hospital | Takatsuki Osaka, Japan, 569-8686Saitama Medical University International Medical Center | Hidaka Saitama, Japan, 350-1298Saitama Prefectural Cancer Center | Ina-machi Saitama, Japan, 362-0806Shizuoka Cancer Center | Nakatogari Shizuoka, Japan, 411-8777National Cancer Center Hospital | Chuo-ku Tokyo, Japan, 104-0045The Cancer Institute Hospital of JFCR | Koto-ku Tokyo, Japan, 135-8550Keio university hospital | Shinjuku-ku Tokyo, Japan, 160-8582National Hospital Organization Kyushu Cancer Center | Fukuoka , Japan, 811-1395National Hospital Organization - Osaka National Hospital - Institute For Clinical Research | Osaka , Japan, 540-0006Accelerium, S. de R.L. de C.V. | Monterrey Nuevo León, Mexico, 64000Centro de Investigacion Clinica de Oaxaca | Oaxaca City , Mexico, 68020Catharina Ziekenhuis | Eindhoven North Brabant, Netherlands, 5623 EJNederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) | Amsterdam North Holland, Netherlands, 1066 CXUniversitair Medisch Centrum Utrecht | Utrecht , Netherlands, 3584 CXAuckland City Hospital | Auckland , New Zealand, 1023St. Olavs hospital | Trondheim Sør-trøndelag, Norway, 7030Sørlandet Sykehus Kristiansand | Kristiansand Vest-agder, Norway, N-4615Oslo universitetssykehus, Radiumhospitalet | Oslo , Norway, 0379Oslo Universitetssykehus Ullevål | Oslo , Norway, 0450Przychodnia Lekarska KOMED | Konin Greater Poland Voivodeship, Poland, 62-500Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza | Brzozów , Poland, 36-200Wojewodzki Szpital Specjalistyczny Nr 4 w Bytomiu Oddzial Onkologii | Bytom , Poland, 41-902COPERNICUS PL sp. z. o. o. Wojewodzkie Centrum Onkologii w Gdansku Ambulatoryjna | Gdansk , Poland, 80-219COPERNICUS Podmiot Leczniczy Sp. z o.o. Wojewodzkie Centrum Onkologii | Gdansk , Poland, 80-219Private Medical Institution "Euromedservice" | Pushkin Sankt-Peterburg, Russia, 196603GBUZ | Chelyabinsk , Russia, 454087Kaluga Regional Clinical Oncology Center | Kaluga , Russia, 248007FSAEI HE I.M Sechenov First MSMU MoH Russia (Sechenovskiy University), | Moscow , Russia, 119991BHI of Omsk Region "Clinical Oncology Dispensary" | Omsk , Russia, 644013BHI of Omsk Region "Clinical Oncology Dispensary" | Omsk , Russia, 644046LLC "Medicina Severnoy Stolitsy" | Saint Petersburg , Russia, 191025LLC "Severo-Zapadny Medical Center" | Saint Petersburg , Russia, 192007Private Healthcare Institution "Clinical Hospital "RZD-Medicine" of St. Petersburg | Saint Petersburg , Russia, 195271LLC "EuroCityClinic" | Saint Petersburg , Russia, 197022FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov | Saint Petersburg , Russia, 197758SHI YR Regional Clinical Oncology Hospital | Yaroslavl , Russia, 150054Narodny Onkologicky Ustav | Bratislava , Slovakia, 833 10Vychodoslovensky onkologicky ustav, a.s. | Košice , Slovakia, 04191Cancercare Rondebosch Oncology | Rondebosch CAPE TOWN, South Africa, 7700Cancercare Langenhoven Drive Oncology Centre | Port Elizabeth Eastern Cape, South Africa, 6045Wits Health Consortium (Pty) Ltd | Johannesburg , South Africa, 2193National Cancer Center | Goyang-si Gyeonggi-do, South Korea, 10408Dong-A University Hospital | Busan , South Korea, 49201Kyungpook National University Chilgok Hospital | Daegu , South Korea, 41404Gachon University Gil Medical Center | Incheon , South Korea, 21565Korea University Anam Hospital | Seoul , South Korea, 02841Seoul National University Hospital | Seoul , South Korea, 03080Severance Hospital, Yonsei University Health System | Seoul , South Korea, 03722Asan Medical Center | Seoul , South Korea, 05505Samsung Medical Center | Seoul , South Korea, 06351Complejo Hospitalario Universitario Santiago de Compostela | Santiago de Compostela A Coruña, Spain, 15706Hospital General Universitario de Elche | Elche Alicante, Spain, 03203ICO L'Hospitalet (Hospital Duran i Reynals) | L'Hospitalet de Llobregat Barcelona, Spain, 08908Hospital Universitario Vall d'Hebron | Barcelona , Spain, 08035Hospital Clinic Barcelona | Barcelona , Spain, 08036Hospital General Universitario Gregorio Marañon | Madrid , Spain, 28007Hospital Universitario Ramon Y Cajal | Madrid , Spain, 28034Hospital Universitario 12 de Octubre | Madrid , Spain, 28041Hospital Universitario Virgen Del Rocio | Seville , Spain, 41013Hospital Clinico Universitario de Valencia | Valencia , Spain, 46010Hospital General Universitario de Valencia | Valencia , Spain, 46014Hospital Universitario Miguel Servet | Zaragoza , Spain, 50009Karolinska Universitetssjukhuset Solna | Solna Stockholms LÄN [se-01], Sweden, 171 64Akademiska sjukhuset | Uppsala Uppsala LÄN [se-03], Sweden, 751 85Norrlands universitetssjukhus | Umeå Västerbottens LÄN [se-24], Sweden, 90185Sahlgrenska Universitetssjukhuset | Gothenburg Västra Götalands LÄN [se14], Sweden, 413 45Department of Pelvic cancer, colorecta section, Karolinska University Hospital | Stockholm , Sweden, 171 76Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City , Taiwan, 807China Medical University Hospital | Taichung , Taiwan, 404National Cheng-Kung University Hospital | Tainan , Taiwan, 704Chi Mei Hospital, Liouying | Tainan , Taiwan, 73657National Taiwan University Hospital | Taipei , Taiwan, 100Taipei Medical University Hospital | Taipei , Taiwan, 11031Taipei Veterans General Hospital | Taipei , Taiwan, 112Chang Gung Medical Foundation-Linkou Branch | Taoyuan , Taiwan, 333Municipal Non-profit Enterprise "City Clinical Hospital #4" of Dnipro City Council | Dnipro , Ukraine, 49102Ivano-Frankivsk National Medical University | Ivano-Frankivsk , Ukraine, 76018MNPE "Prykarpatski Clinical Oncological Center" of Ivano-Frankivsk Regional Council" | Ivano-Frankivsk , Ukraine, 76018Communal enterprise "Kryvyi Rih Oncology Dispensary" of Dnipropetrovsk Regional Council | Kryvyi Rih , Ukraine, 50048Freeman Hospital | Newcastle upon Tyne HIGH Heaton, United Kingdom, NE7 7DNRoyal Marsden NHS Foundation Trust | Sutton Surrey, United Kingdom, SM2 5PTHeartlands Hospital | Birmingham , United Kingdom, B9 5SSHammersmith Hospital, Imperial College Healthcare NHS Trust | London , United Kingdom, W12 0HSHammersmith Hospital | London , United Kingdom, W6 8RFChurchill Hospital - Oncology | Oxford , United Kingdom, OX3 7LE
Investigators
Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full Text)
Documents provided by Pfizer: Study Protocol  May 30, 2024Documents provided by Pfizer: Statistical Analysis Plan  May 6, 2024