A Study Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer. (NAUTICALCRC)

A Multicenter, Randomized, Open-label, 2-arm, Phase II Study With a Safety lead-in Phase Evaluating the Combination of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or Infusional 5-fluorouracil (5-FU)/Folinic Acid (FA)/Irinotecan (FOLFIRI)/Cetuximab in Chinese Patients With BRAF V600E Mutant Metastatic Colorectal Cancer.

Encorafenib is currently being developed (with or without binimetinib), in combination with cetuximab, for the treatment of adult patients with B-RAF proto-oncogene, serine/threonine kinase V600E mutant (BRAF V600E) metastatic colorectal cancer (mCRC), who have received prior systemic therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer; BRAF V600E
• Intervention / Treatment: Drug: Encorafenib; Drug: Cetuximab; Drug: FOLFIRI

• Study Type: Interventional
• Enrollment (Estimated): 103
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shankar Balaratnam; Phone Number: +44 (0) 7770 542678; Email: shankar.balaratnam@pierre-fabre.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100036
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Medical University - Fujian Provincial Cancer Hospital
    • Xiamen, Fujian, China, 361001
      • The First Affiliated Hospital of Xiamen University
  • Guangdong
    • Foshan, Guangdong, China, 528010
      • The First People's Hospital of Foshan
    • Guangzhou, Guangdong, China, 510095
      • Cancer Center of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510655
      • The Sixth Affiliated Hospital Sun Yat-Sen University
    • Shantou, Guangdong, China, 515041
      • Cancer Hospital affiliated to Shantou University Medical College
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital
  • Hebei
    • Baoding, Hebei, China, 071000
      • The Affiliated Hospital of Hebei University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150040
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China, 430022
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • The First People's Hospital of Changzhou
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341001
      • First Affiliated hospital of GANNAN Medical University
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330006
      • The Second Affiliated Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Jinzhou, Liaoning, China, 121011
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China, 110042
      • Liaoning cancer Hospital & Institute
  • Shaanxi
    • Xi'an, Shaanxi, China, 710068
      • Shaanxi Provincial People's Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital Fudan University
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China, 200120
      • Shanghai East Hospital, Tongji University
  • Sichuan
    • Neijiang, Sichuan, China, 641000
      • The Second People's Hospital of Neijiang
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital - Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria for Molecular Prescreening:

The following inclusion criteria must be met for a participant to be eligible to undergo molecular tumor prescreening:

• Chinese male or female participant with age ≥18 years at the time of informed consent.
• Histologically- or cytologically-confirmed colorectal cancer (CRC) that is metastatic.
• Eligible to receive cetuximab per Chinese approved label with regard to tumor Rat Sarcoma Viral Oncogene Homologue (RAS) mutation status (i.e. approved for Rat Sarcoma Viral Oncogene Homologue Wild Type(RAS wt) status).
• Able to provide a sufficient amount of representative tumor specimen for central prospective laboratory testing of B-RAF Proto-oncogene, Serine/threonine Kinase (BRAF) mutation status and also retrospective RAS wt status and Microsatellite Instability (MSI) testing.

Inclusion Criteria for Treatment Period:

The following inclusion criteria must be met for a participant to be eligible for this study:

• Chinese male or female participant with age ≥18 years at time of informed consent.
• Histologically or cytologically confirmed CRC that is metastatic and unresectable at time of study entry (i.e. not suitable for complete surgical resection at screening).
• Presence of a BRAF V600E mutation in tumor tissue previously determined by a local assay at any time before screening or by the central laboratory.

NOTE: Other protocol defined Inclusion criteria may apply

Exclusion Criteria for Molecular Prescreening:

Participants meeting any of the following criteria are not eligible to undergo molecular tumor prescreening:

• Prior anti-Epidermal Growth Factor Receptor (anti-EGFR) treatment
• More than two prior regimens in the metastatic setting.
• Known contraindication to receive cetuximab or irinotecan at the planned dose according to the most recent cetuximab and irinotecan local label.
• Known history of Gilbert's syndrome or is known to have any of the following genotypes: uridine 5'-diphospho-glucuronosyltransferase (UGT)1A1*6/*6, UGT1A1*28/*28 or UGT1A1*6/*28.
• Leptomeningeal disease.

Exclusion Criteria for Treatment Period:

• Prior treatment with any Proto oncogene Serine/threonine-Protein Kinase (RAF) inhibitor, cetuximab, panitumumab or other EGFR inhibitors.
• Symptomatic brain metastasis.
• Leptomeningeal disease.
• Use of any herbal medications/supplements or any medications or foods that are moderate or strong inhibitors or inducers of cytochrome P450 (CYP)3A4/5 ≤1 week before the start of study intervention.
• Known history of acute or chronic pancreatitis within 6 months before the start of study intervention.

NOTE: Other protocol defined Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Encorafenib and cetuximab; Safety Lead-in (SLI) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly Randomized (Phase II) phase: 28 day cycles of encorafenib once daily (QD) 300 mg (4 x 75 mg oral capsule) and cetuximab 400 mg/m² initial dose (120-minute infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly	Drug: Encorafenib; oral hard capsule; Other Names: LGX818; Braftovi®; PF-07263896; W0090; ONO-7702; Drug: Cetuximab; intravenous infusion; Other Names: C225; Erbitux®
Experimental: Irinotecan and cetuximab or FOLFIRI and cetuximab; Randomized (Phase II) phase: Either irinotecan and cetuximab or FOLFIRI and cetuximab in 28 day cycles. Irinotecan and cetuximab: irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks and; cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly OR FOLFIRI and cetuximab: irinotecan 180 mg/m² (90-minute intravenous infusion or to study site standards) every 2 weeks; Folinic acid 400 mg/m² (120-minute infusion or to study site standards) or maximal dose tolerated in a prior regimen every 2 weeks; 5-FU 400 mg/m² initial dose bolus (not to exceed 15 minutes), then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46 to 48 hours) continuous infusion or maximal dose tolerated in a prior regimen every 2 weeks and; cetuximab 400 mg/m² initial dose (120-minute intravenous infusion), then 250 mg/m² (60-minute infusion) thereafter once weekly	Drug: Encorafenib; oral hard capsule; Other Names: LGX818; Braftovi®; PF-07263896; W0090; ONO-7702; Drug: Cetuximab; intravenous infusion; Other Names: C225; Erbitux®; Drug: FOLFIRI; Combination of: irinotecan ( also known as: Camptosar, Camptothecin-11 and CPT-11) intravenous infusion, folinic acid (also known as: 5-formyl tetrahydrofolic acid and leucovorin) intravenous infusion, and 5-FU (also known as; fluorouracil) intravenous bolus/intravenous infusion; Other Names: Folinic acid + Fluorouracil + Irinotecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Lead-in Phase: Incidence of Dose Limiting Toxicities (DLTs) during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI)		Day 1 to Day 28
Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to treatment received) Independent Central Review (BICR)	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) v1.1., or death due to any cause	Day 1 through to study completion, approximately from 12 to 29 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Lead-in Phase: Type and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03		Informed consent through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations	Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported.	Day 1 through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes in vital signs from baseline of vital sign examinations.	Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 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%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: 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% decrease from baseline; Body temperature [°C]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported.	Day 1 through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of 12-lead electrocardiograms (ECGs)	12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms) : increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms. Heart rate (beats/min) : increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported.	Day 1 through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.	Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. 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. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.	Day 1 through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of development of of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations	This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at 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.	Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Performance status assessment using the Eastern Co-operative Oncology Group (ECOG) performance status scale	Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death	Screening (Day -28 to -1) through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Incidence of dose interruptions, dose modifications and discontinuations due to adverse events (AEs)		Day 1 until end of treatment, approximately 1 year
Safety Lead-in Phase: Plasma concentrations of encorafenib		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Serum concentrations of cetuximab		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Safety Lead-in Phase: Objective response rate (ORR)	Objective response rate (ORR) defined as the proportion of participants with a best overall best response of either complete response (CR) or partial response (PR) as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	Day 1 through to study completion, approximately from 18 to 35 months
Safety Lead-in Phase: Duration of Response (DOR) (months); defined for responders complete response (CR) or partial response (PR) only, is duration of time from the date of the first documented response to the earliest date of disease progression	Duration of response, defined as the time from first documented response (complete response or partial response) to the earliest date of disease progression as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, or death due to underlying disease.	Day 1 through to study completion, approximately from 18 to 35 months
Randomized Phase 2: Progression-free survival (PFS)	Progression-free survival defined as the interval of time between the date of randomization to the earliest date of disease progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Overall Response Rate (ORR)	Overall response rate (for confirmed and unconfirmed responses) defined as the proportion of participants with a confirmed (resp. unconfirmed) best overall response of either complete response or partial response, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Duration of Response (DOR)	Duration of response defined as the time from the date of the first documented response (complete response or partial response) to the earliest date of disease progression, as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Disease control rate (DCR)	Disease control rate (DCR), defined as the proportion of participants with a best overall response of either complete response, partial response or stable disease (SD), as determined by Blinded (to treatment received) Independent Central Review (BICR) and investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Time to Response (TTR)	Time to Response (for confirmed and unconfirmed responses) is defined as the time between date of randomization until first documented response of complete response (CR) or partial response (PR).	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Overall Survival (OS)	Overall survival is defined as time from randomization until date of death due to any cause	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Type and severity of adverse events (AEs) and serious adverse events (SAEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03		Informed consent date through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes from baseline of physical examinations	Standard physical examinations on cardiovascular, respiratory, gastrointestinal, dermatological, ophthalmological and neurological systems will be performed and will be evaluated based on normal/abnormal and clinical significance observations. Number of participants with TEAEs related to abnormal or clinical significance observations to the physical examinations after the start of study drug will be reported	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in vital signs from baseline.	Clinically notable elevated values: Systolic blood pressure (BP): ≥ 160 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%; Body temperature(°C) ≥ 37.5°C). Clinically notable low values: 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% decrease from baseline; Body temperature [°C]: ≤ 36 °C. Number of participants with TEAEs related to notable changes to the vital signs after the start of study drug will be reported.	Day 1 through to study completion, approximately from 12 to 29 months
Incidence of treatment-emergent adverse events (TEAEs) related to notable or abnormal changes to electrocardiogram evaluations from baseline	12-lead ECGs will be obtained using an internationally recognized 12-lead cardiograph. Clinically notable ECG values: QT (ms) and QT interval (ms) corrected for heart rate using Fridericia's formula (QTcF) intervals (ms): increase from baseline > 30 ms; increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms; Heart rate (beats/min): increase from baseline > 25% to a value > 100 bpm, decrease from baseline > 25% and to a value < 50 bpm. Number of participants with TEAEs related to abnormal or notable changes to ECG parameters after the start of study drug will be reported.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Incidence of treatment-emergent adverse events (TEAEs) related to notable changes in clinical safety laboratory parameters from baseline.	Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. 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. Clinically notable shift is defined as a worsening from baseline by at least 2 grades, or to grade 3 or above.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Incidence of development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma by dermatological examinations	This is to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and new primary melanoma, as these have been reported to occur with selective BRAF inhibitor treatment. This assessment will be performed at 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.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: To determine the performance status using the Eastern Co-operative Oncology Group (ECOG) performance status scale.	Scale with a range from 0 to 5 with lower score mean a lower functional impairment, 5 corresponding to death	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: To determine if there is any change from baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire scores	EORTC QLQ-C30 consist 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 will be scored (0 to 100). High scores represents a high health/quality of life	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: To determine if there is any change from baseline in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire scores.	EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (VAS). The descriptive system has five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each is 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 describes the participant's health state.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: To determine if there is any change from baseline in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) questionnaire scores	FACT-C is a validated quality of life questionnaire for patient reported outcome assessment. FACT-C consists 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.	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: To determine if there is any changes in the Patient Global Impression of Change (PGIC) questionnaire scores.	PGIC will ask participants to evaluate their CRC symptoms since starting study intervention according to a seven-point verbal rating scale (VRS): 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse	Day 1 through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Plasma concentrations of encorafenib		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Serum concentrations of cetuximab		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2; Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib area under curve (AUC) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab area under curve (AUC) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib minimum concentration (Cmin) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab minimum concentration (Cmin) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Pharmacokinetic (PK) parameter derived from plasma concentration of encorafenib maximum concentration (Cmax) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Pharmacokinetic (PK) parameter derived from serum concentration of cetuximab maximum concentration (Cmax) in Chinese participants		Day 1 of Cycles 1 and 2; Each cycle = 28 days
Randomized Phase 2: Population pharmacokinetic (PK) analysis using the ARRAY 818 302 study PK data		Day 1 through to study completion, approximately from 12 to 29 months

Other Outcome Measures

Outcome Measure	Time Frame
Randomized Phase 2: Changes from baseline in blood Carcinoembryonic Antigen (CEA) and Cancer Antigen 19-9 (CA19-9) at the beginning of each cycle and at the end of treatment	Screening (Day -28 to -1) through to study completion, approximately from 12 to 29 months
Randomized Phase 2: Microsatellite Instability (MSI) status in Formalin-fixed and Paraffin Embedded (FFPE) samples using established Polymerase Chain Reaction (PCR) assays in tumor sample versus germline control at screening	Screening (Day -28 to Day -1)

Collaborators and Investigators

• Sponsor: Pierre Fabre Medicament
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Principal Investigator: Shen Lin, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Actual): December 19, 2023
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: August 5, 2021
• First Posted (Actual): August 13, 2021

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Cancer; BRAF V600E
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Fluorouracil; Irinotecan; Cetuximab
• Other Study ID Numbers: W00090GE202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No