A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer

Sponsor
Tianjin Medical University Cancer Institute and Hospital
Study ID
NCT07506109
Phase
PHASE2
Status
Recruiting
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Conditions

  • BRAF V600E
  • Cetuximab
  • Colorectal Cancer
  • Dabrafenib
  • Ipilimumab N01
  • MSS (Microsatellite Stable)
  • Sintilimab

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ipilimumab N01 — DRUG
    1mg/kg ivd，q6w or 3mg/kg ivd，q12w followed by maintenance therapy with Ipilimumab N01 1 mg/kg ivd, q6w. The specific dosage and administration schedule should be referred to the relevant study design.
  • Sintilimab — DRUG
    2mg/kg ivd, q3w
  • Cetuximab — DRUG
    500mg/m2 ivd，q2w
  • Dabrafenib — DRUG
    150mg po bid

Study Details

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.

Key Dates

Start date
Mar 1, 2026
Status verified
Dec 2025
Primary completion
Dec 31, 2027
Completion
Jun 30, 2028

Study Design

Enrollment
49 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: First-line cohort
    Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib
  • Experimental: Second-line cohort
    Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib

Primary Outcome Measure

Progression-Free Survival (PFS) [ Time Frame: up to 2 years ]

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