Tolerability and Safety of Vemurafenib, Cetuximab Combined With Camrelizumab for BRAF V600E-mutated /MSS Metastatic Colorectal Cancer

NCT05019534 | Unknown Phase 1

• 1 other identifier: ChiECRCT20210210
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

BRAF mutation exists in about 10-12% of colorectal cancer, among which BRAF V600E mutation is the most common type, which is an important biomarker for predicting the prognosis and precise treatment efficacy of metastatic colorectal cancer (mCRC). The prognosis of metastatic colorectal cancer with BRAF V600E mutation is very poor, with OS of about 6-9 months. Previous studies have shown that single anti-BRAF inhibitor are ineffective, while multi-target inhibitions of Ras-Raf -MEK pathway is a possible effective strategy for BRAF V600E-mutant mCRC. Currently, the proven effective regimens include the VIC regimen (Vemurafenib + cetuximab + Irinotecan) and BEACON regimen (Encorafenib+ cetuximab +/- Binimetinib) from the SWOGS1406 study. Furthermore, BRAF inhibitor +MEK inhibitor combined with PD-1 monoclonal antibody has been shown to be an effective strategy in BRAF V600E-mutant malignant melanoma, which promote the study of the regimens for the treatment of BRAF V600E-mutant mCRC. Increasing basic and clinical studies have shown that cetuximab has ADCC effect, induces immunogenic cell death, promotes immune cell infiltration and other immunomodulatory effects, and has a synergistic effect with PD-1 monoclonal antibody in colorectal cancer. Based on those theories, we conducted the phase I study to explore the safety and preliminary efficacy of the regimen of Vemurafenib (BRAFi) plus cetuximab (EGFRi) combined with PD-1 monoclonal antibody in BRAF V600E-mutant /MSS type mCRC.

Conditions

BRAF V600E-mutated /MSS Metastatic Colorectal Cancer; Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Evaluate tolerability and safety and identify the recommended Phase 2 dose(RP2D)

  Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28)

Secondary Outcomes (5)

• Object Response Rate (ORR)

  up to 24 weeks

• Disease Control Rate (DCR)

  up to 24 weeks

• Progression Free Survival (PFS)

  up to 1 year

• Overall Survival (OS)

  up to 3 year

• Preliminary efficacy

  up to 1 year

Study Arms (1)

Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)

EXPERIMENTAL

Cetuximab and Camrelizumab in the fixed dose Vemurafenib have two dose groups: 960mg qd or 960mg bid

Drug: Vemurafenib Oral Tablet [Zelboraf]; Drug: Cetuximab Injection [Erbitux]; Drug: Camrelizumab

Interventions

Vemurafenib Oral Tablet [Zelboraf] DRUG

Vemurafenib 960mg qd or 960mg bid (2 cohorts)

Also known as: Zelboraf

Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)

Cetuximab Injection [Erbitux] DRUG

Cetuximab 500mg/m2 Q2W

Also known as: Erbitux

Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)

Camrelizumab DRUG

Camrelizumab 200mg Q2W

Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Participants must have histologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria
• Presence of BRAF V600E in tumor tissue determined by local assay at any time prior to screening and confirmed by central laboratory. And confirmation of MSS or pMMR status from immunohistochemistry or PCR or NGS;
• Prior treatment with at least one systemic treatment (chemotherapy or target therapy) for mCRC, and prior treatment did not include cetuximab
• Adequate organ and marrow function:
• ①Hemoglobin (Hb) ≥ 90 g/L；Platelets (PLT) ≥ 75 x 10\^9/L；Neutrophil ≥1.5 x 10\^9/L
• ②Total bilirubin ≤ 1.5 x upper limit of normal (ULN)；Aspartate aminotransferase (AST) ≤3 x ULN ；Alanine aminotransferase (ALT) ≤3 x ULN
• ③Serum creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50 mL/min at screening
• ④INR, APTT, and PT≤ 1.5 x ULN
• ⑤Serum albumin≥ 28 g/L
• ⑥ECG showed no evident abnormality
• Written informed consent

You may not qualify if:

• Known hypersensitivity or contraindication to any component of cetuximab or PD-1 monoclonal antibody or macromolecular protein reagent.
• A history of other malignancies with a disease-free survival of less than 5 years, with the following exceptions: adequately treated basal or squamous cell skin cancer, carcinoma in-situ of the cervix, and gastrointestinal tumors treated curatively with endoscopic mucosectomy;
• Any active autoimmune disease or a history of autoimmune disease
• Use of immunosuppressive medications or glucocorticoid therapy ≤2 weeks prior to entry
• Uncontrolled active infection requiring antibiotics
• Known history of HIV infection or active hepatitis
• Severe complications, including any of the following:
• ①Massive gastrointestinal bleeding, perforation, or gastrointestinal obstruction
• ②Symptomatic heart disease
• ③Uncontrolled diabetes and hypertension
• ④Uncontrolled diarrhea
• Women who are pregnant or lactating and people who do not agree to avoid pregnancy
• Patients with serious psychiatric that may interfere treatment.
• Other conditions which are inappropriate to participate in the study confirmed by investigators.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (1)

Sichuan University West China Hospital

Chengdu, Sichuan, 610044, China

RECRUITING

Related Publications (1)

• Wei GX, Zhou YW, Cao P, Leng WB, Wang L, Tang J, Qiu M. Vemurafenib, cetuximab and camrelizumab in BRAF V600E-mutated/MSS metastatic colorectal cancer. J Transl Med. 2025 Nov 12;23(1):1274. doi: 10.1186/s12967-025-07312-6.

  PMID: 41225509 DERIVED

MeSH Terms

Interventions

Vemurafenib; Cetuximab; camrelizumab

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Meng Qiu

CONTACT

+862885423203; qiumeng33@hotmail.com

Weibing Leng, Ph.D

CONTACT

+8618980601776; s103470@stu.scu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: August 25, 2021
• Study Start: August 15, 2021
• Primary Completion: August 1, 2022
• Study Completion: December 1, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)