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

NCT07506109 | Not Yet Recruiting Phase 2

• 1 other identifier: SICD-BRAF
• Study Type: interventional
• Target: 49
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from study entry until the first occurrence of disease progression or death from any cause, whichever comes first. If a subject does not experience disease progression during the trial, PFS is defined as the date of the last confirmed progression-free survival assessment for that subject.

  up to 2 years

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  up to 1 year

• Objective Response Rate (ORR)

  up to 1 year

• Overall Survival (OS)

  up to 3 years

• Treatment-Related Adverse Events (TRAE)

  up to 3 years

Study Arms (2)

First-line cohort

EXPERIMENTAL

Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib

Drug: Ipilimumab N01; Drug: Sintilimab; Drug: Cetuximab; Drug: Dabrafenib

Second-line cohort

EXPERIMENTAL

Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib

Drug: Ipilimumab N01; Drug: Sintilimab; Drug: Cetuximab; Drug: Dabrafenib

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.

Also known as: IBI-310

First-line cohort; Second-line cohort

Sintilimab DRUG

2mg/kg ivd, q3w

Also known as: IBI-308

First-line cohort; Second-line cohort

Cetuximab DRUG

500mg/m2 ivd，q2w

First-line cohort; Second-line cohort

Dabrafenib DRUG

150mg po bid

First-line cohort; Second-line cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Spinocerebellar Degenerations

Interventions

sintilimab; Cetuximab; dabrafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ting Deng PhD

CONTACT

+86 18526812877; 18526812877@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2026
• First Posted: April 1, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 1, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share