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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Sintilimab; BRAF V600E; Cetuximab; MSS (Microsatellite Stable); Dabrafenib; Ipilimumab N01
• Intervention / Treatment: Drug: Ipilimumab N01; Drug: Sintilimab; Drug: Cetuximab; Drug: Dabrafenib

• Study Type: Interventional
• Enrollment (Estimated): 49
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ting Deng PhD; Phone Number: +86 18526812877; Email: 18526812877@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Not yet recruiting
      • Peking Union Medical College Hospital
      • Contact: Xicheng Wang, Prof.; Phone Number: 010-69158370; Email: xicheng_wang@hotmail.com
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Zhenyu Lin; Phone Number: 027-85871982; Email: whxhlzy@hust.edu.cn
  • Sichuan
    • Chengdu, Sichuan, China
      • Not yet recruiting
      • West China Hospital Sichuan University
      • Contact: Meng Qiu, MD; Phone Number: 028-85423203; Email: qiumeng33@hotmail.com
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Ting Deng, PhD; Phone Number: +86 18526812877; Email: 18526812877@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Provided written informed consent.
2. Age ≥ 18 years.
3. Histologically or pathologically confirmed colorectal adenocarcinoma.
4. Documented microsatellite stable (MSS) and BRAF V600E mutation by prior genomic testing.
5. Locally advanced unresectable disease or distant metastasis.
6. No prior treatment with BRAF/MEK/ERK inhibitors, EGFR inhibitors, or immune checkpoint inhibitors (ICI).
7. Presence of measurable target lesions per RECIST 1.1.
8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1.

9. Adequate organ function, based on the following laboratory values obtained within 7 days prior to Cycle 1 Day 1:

   1. Hemoglobin ≥ 9.0 g/dL.
   2. Absolute neutrophil count ≥ 1,500/mm³ (≥ 1.5 × 109/L).
   3. Platelet count ≥ 80,000/mm³ (≥ 80 × 109/L).
   4. Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN).
   5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
   6. Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min.
10. Willing and able to comply with study procedures and visit schedule.

Exclusion Criteria:

1. Received any approved or investigational systemic anti-tumor therapy within 4 weeks prior to enrollment.
2. Underwent any surgery or invasive procedure within 4 weeks prior to study initiation (exceptions include venous catheter placement and paracentesis/drainage).
3. 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).
4. Presence of severe comorbidities or serious medical conditions.
5. Pregnant or breastfeeding females.
6. The investigator deems the patient unsuitable for participation in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: First-line cohort; Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib	Drug: Ipilimumab N01; 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.; Other Names: IBI-310; Drug: Sintilimab; 2mg/kg ivd, q3w; Other Names: IBI-308; Drug: Cetuximab; 500mg/m2 ivd，q2w; Drug: Dabrafenib; 150mg po bid
Experimental: Second-line cohort; Ipilimumab N01+Sintilimab+Cetuximab+Dabrafetinib	Drug: Ipilimumab N01; 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.; Other Names: IBI-310; Drug: Sintilimab; 2mg/kg ivd, q3w; Other Names: IBI-308; Drug: Cetuximab; 500mg/m2 ivd，q2w; Drug: Dabrafenib; 150mg po bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	DCR: The percentage of patients with a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) that is maintained for at least 4 weeks, among all patients evaluable for efficacy.	up to 1 year
Objective Response Rate (ORR)	ORR: The proportion of patients who achieve a reduction in tumor size of a predefined magnitude that is maintained for a specified duration, including cases of CR and PR. Tumor objective response will be assessed in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. All subjects must have measurable tumor lesions at baseline. Efficacy assessments will be categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) based on RECIST v1.1 criteria.	up to 1 year
Overall Survival (OS)	OS is defined as the time from study entry to death from any cause. For subjects who are still alive at the final follow-up, OS will be censored at the time of the final follow-up. For lost-to-follow-up subjects, OS will be censored at the time of the last confirmed alive assessment prior to loss to follow-up. OS for censored subjects is defined as the time from study entry to the censoring date.	up to 3 years
Treatment-Related Adverse Events (TRAE)	Treatment-Related Adverse Events (TRAE) as assessed by CTCAE v5.0, including serious adverse events (SAEs)	up to 3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 9, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Genetic Diseases, Inborn; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neurodegenerative Diseases; Colonic Diseases; Heredodegenerative Disorders, Nervous System; Spinal Cord Diseases; Cerebellar Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Colorectal Neoplasms; Spinocerebellar Degenerations; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Cetuximab; dabrafenib; sintilimab
• Other Study ID Numbers: SICD-BRAF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No