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

NCT ID: NCT05019534

Last Updated: 2022-05-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-15
• Study Completion Date: 2022-12-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vemurafenib, Cetuximab Combined With Camrelizumab (VCC)

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

Group Type: EXPERIMENTAL

Vemurafenib Oral Tablet [Zelboraf]

Intervention Type: DRUG

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

Cetuximab Injection [Erbitux]

Intervention Type: DRUG

Cetuximab 500mg/m2 Q2W

Camrelizumab

Intervention Type: DRUG

Camrelizumab 200mg Q2W

Interventions

Vemurafenib Oral Tablet [Zelboraf]

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

Intervention Type: DRUG

Cetuximab Injection [Erbitux]

Cetuximab 500mg/m2 Q2W

Intervention Type: DRUG

Camrelizumab

Camrelizumab 200mg Q2W

Intervention Type: DRUG

Other Intervention Names

Zelboraf; Erbitux

Eligibility Criteria

Inclusion Criteria

1. Male or female ≥ 18 years of age

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

3. 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

4. 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;

5. Prior treatment with at least one systemic treatment (chemotherapy or target therapy) for mCRC, and prior treatment did not include cetuximab

6. 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

7. Written informed consent

Exclusion Criteria

1. Known hypersensitivity or contraindication to any component of cetuximab or PD-1 monoclonal antibody or macromolecular protein reagent.

2. 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;

3. Any active autoimmune disease or a history of autoimmune disease

4. Use of immunosuppressive medications or glucocorticoid therapy ≤2 weeks prior to entry

5. Uncontrolled active infection requiring antibiotics

6. Known history of HIV infection or active hepatitis

7. Severe complications, including any of the following:

• ①Massive gastrointestinal bleeding, perforation, or gastrointestinal obstruction
• ②Symptomatic heart disease
• ③Uncontrolled diabetes and hypertension
• ④Uncontrolled diarrhea

8. Women who are pregnant or lactating and people who do not agree to avoid pregnancy

9. Patients with serious psychiatric that may interfere treatment.

10. Other conditions which are inappropriate to participate in the study confirmed by investigators.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Meng Qiu

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sichuan University West China Hospital

Chengdu, Sichuan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Meng Qiu

Role: CONTACT

qiumeng33@hotmail.com

+862885423203

Weibing Leng, Ph.D

Role: CONTACT

s103470@stu.scu.edu.cn

+8618980601776

Facility Contacts

Weibing Leng, Ph.D

Role: primary

s103470@stu.scu.edu.cn

+8618980601776

Other Identifiers

ChiECRCT20210210

Identifier Type: -

Identifier Source: org_study_id