A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer
Recruiting · NCT07506109 · Interventional (participants receive a specific treatment) · Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
Colorectal cancer (CRC) is the second leading cause of cancer-related death globally. BRAF V600E mutations occur in approximately 12% of metastatic CRC (mCRC) patients, conferring an extremely poor prognosis with a median overall survival (OS) of only 11 months for standard chemotherapy. Most BRAF V600E-mutant mCRC are microsatellite stable (MSS) and do not benefit from single-agent PD-1/PD-L1 inhibition. Preclinical and clinical evidence indicates that BRAF inhibition in combination with EGFR blockade can induce DNA damage, trigger a deficient mismatch repair (dMMR) phenotype, and increase tumor mutational burden (TMB), thereby sensitizing MSS tumors to immune checkpoint inhibition. This provides a strong rationale for combining BRAF/EGFR inhibitors with anti-PD-1 and anti-CTLA-4 immunotherapy. This is a single-arm, open-label, Phase II clinical trial. The primary objective is to evaluate the efficacy and safety of the triplet combination of sintilimab (anti-PD-1), ipilimumab N01 (anti-CTLA-4), cetuximab (anti-EGFR), and dabrafenib (BRAF inhibitor) in patients with MSS, BRAF V600E-mutant mCRC.
Who can take part
Inclusion criteria
- Provided written informed consent.
- Age ≥ 18 years.
- Histologically or pathologically confirmed colorectal adenocarcinoma.
- Documented microsatellite stable (MSS) and BRAF V600E mutation by prior genomic testing.
- Locally advanced unresectable disease or distant metastasis.
- No prior treatment with BRAF/MEK/ERK inhibitors, EGFR inhibitors, or immune checkpoint inhibitors (ICI).
- Presence of measurable target lesions per RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.
- Adequate organ function, based on the following laboratory values obtained within 7 days prior to Cycle 1 Day 1:
- Hemoglobin ≥ 9.0 g/dL.
- Absolute neutrophil count ≥ 1,500/mm³ (≥ 1.5 × 109/L).
- Platelet count ≥ 80,000/mm³ (≥ 80 × 109/L).
- Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN).
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
- Willing and able to comply with study procedures and visit schedule.
Exclusion criteria
- Received any approved or investigational systemic anti-tumor therapy within 4 weeks prior to enrollment.
- Underwent any surgery or invasive procedure within 4 weeks prior to study initiation (exceptions include venous catheter placement and paracentesis/drainage).
- Multiple primary malignancies (exceptions include completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, intramucosal carcinoma, superficial bladder cancer, or any other cancer that has been in complete remission for at least 3 years).
- Presence of severe comorbidities or serious medical conditions.
- Pregnant or breastfeeding females.
- The investigator deems the patient unsuitable for participation in this study.
Where it is running
4 locations listed.
- Peking union medical college hospital - Beijing, Beijing Municipality, China
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology - Wuhan, Hubei, China
- West China Hospital Sichuan University - Chengdu, Sichuan, China
- Tianjin Medical University Cancer Institute and Hospital - Tianjin, Tianjin Municipality, China