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

  • STATUS
    Recruiting
  • days left to enroll
    57
  • participants needed
    12
  • sponsor
    West China Hospital
Updated on 5 June 2022

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.

Details
Condition BRAF V600E-mutated /MSS Metastatic Colorectal Cancer, Vemurafenib (BRAFi) Plus Cetuximab (EGFRi) Combined With PD-1 Monoclonal Antibody
Treatment Camrelizumab, Vemurafenib Oral Tablet [Zelboraf], Cetuximab Injection [Erbitux]
Clinical Study IdentifierNCT05019534
SponsorWest China Hospital
Last Modified on5 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

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
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