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

Sponsor
West China Hospital
Study ID
NCT05019534
Phase
PHASE1
Status
Unknown

Conditions

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

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Vemurafenib Oral Tablet [Zelboraf] — DRUG
    Vemurafenib 960mg qd or 960mg bid (2 cohorts)
  • Cetuximab Injection [Erbitux] — DRUG
    Cetuximab 500mg/m2 Q2W
  • Camrelizumab — DRUG
    Camrelizumab 200mg Q2W

Study Details

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.

Key Dates

Start date
Aug 15, 2021
Status verified
May 2022
Primary completion
Aug 1, 2022
Completion
Dec 1, 2022

Study Design

Enrollment
12 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)
    Cetuximab and Camrelizumab in the fixed dose Vemurafenib have two dose groups: 960mg qd or 960mg bid

Primary Outcome Measure

Evaluate tolerability and safety and identify the recommended Phase 2 dose(RP2D) [ Time Frame: Subjects will be treated and observed for dose-limiting toxicity(DLT) through the end of the first cycle (Days 1-28) ]

Central Contacts