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.

NCT05004350 | Completed Phase 2 Results DMC

• 1 other identifier: W00090GE202
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 34

Brief Summary

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.

Conditions

BRAF V600E; Metastatic Colorectal Cancer

Keywords

BRAF V600E; Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)

  DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm.

  Cycle 1 (up to 28 days)

• Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date

  PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.

  From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks

• Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis

  PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.

  From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks

Secondary Outcomes (53)

• Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR

  Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks

• Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator

  Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks

• Safety Lead-in Phase: Duration of Response (DOR) Per BICR

  From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks

• Safety Lead-in Phase: Duration of Response (DOR) Per Investigator

  From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks

• Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment

  Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks

Study Arms (2)

Encorafenib and cetuximab

EXPERIMENTAL

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; Drug: Cetuximab

Irinotecan and cetuximab or FOLFIRI and cetuximab

EXPERIMENTAL

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; Drug: Cetuximab; Drug: FOLFIRI

Interventions

Encorafenib DRUG

oral hard capsule

Also known as: Braftovi®, PF-07263896, W0090, LGX818, ONO-7702

Encorafenib and cetuximab; Irinotecan and cetuximab or FOLFIRI and cetuximab

Cetuximab DRUG

intravenous infusion

Also known as: Erbitux®, C225

Encorafenib and cetuximab; Irinotecan and cetuximab or FOLFIRI and cetuximab

FOLFIRI DRUG

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

Also known as: Folinic acid + Fluorouracil + Irinotecan

Irinotecan and cetuximab or FOLFIRI and cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Pierre Fabre Medicament: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (34)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100036, China

Location

Peking Union Medical College Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100730, China

Location

Fujian Medical University - Fujian Provincial Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361001, China

Location

The First People's Hospital of Foshan

Foshan, Guangdong, 528010, China

Location

Cancer Center of Guangzhou Medical University

Guangzhou, Guangdong, 510095, China

Location

The Sixth Affiliated Hospital Sun Yat-Sen University

Guangzhou, Guangdong, 510655, China

Location

Cancer Hospital Affiliated to Shantou University Medical College

Shantou, Guangdong, 515041, China

Location

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

Location

The Affiliated Hospital of Hebei University

Baoding, Hebei, 071000, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150040, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Union Hospital Tongji medical college Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

Location

The First People's Hospital of Changzhou

Changzhou, Jiangsu, 213003, China

Location

First Affiliated Hospital of Gannan Medical University

Ganzhou, Jiangxi, 341001, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The First Affiliated Hospital of Jinzhou Medical University

Jinzhou, Liaoning, 121011, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

Location

Shaanxi Provincial People's Hospital

Xi'an, Shaanxi, 710068, China

Location

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200092, China

Location

Shanghai East Hospital, Tongji University

Shanghai, Shanghai Municipality, 200120, China

Location

The Second People's Hospital of Neijiang

Neijiang, Sichuan, 641000, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

The First Affiliated Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

Sir Run Run Shaw Hospital - Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310016, China

Location

Related Publications (1)

• Xicheng W, Yanhong D, Yanqiao Z, Tianshu L, Xianglin Y, Jianwei Y, Tao Z, Aimin Z, Yu L, Li H, Feng Y, Hong Z, Yi B, Isabelle K, Jean-Claude V, Melanie G, Angela G, Jian L, Lin S. A Randomized Trial of Encorafenib and Cetuximab Versus Irinotecan/Cetuximab or FOLFIRI/Cetuximab in Chinese Patients With BRAFV600E Mutant Metastatic Colorectal Cancer: The NAUTICAL Study. Cancer Med. 2026 Mar;15(3):e71697. doi: 10.1002/cam4.71697.

  PMID: 41852303 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

encorafenib; Cetuximab; IFL protocol; Leucovorin; Fluorouracil; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids

Results Point of Contact

• Title: Isabelle Klauck, MD/Study Director
• Organization: Pierre Fabre Médicament

isabelle.klauck@pierre-fabre.com

+33 (0)7 87 29 60 13

Study Officials

• Shen Lin, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: August 13, 2021
• Study Start: September 14, 2021
• Primary Completion: December 19, 2023
• Study Completion: December 7, 2024
• Last Updated: April 30, 2026
• Results First Posted: April 30, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (34)