Sintilimab + ipilimumab N01 with cetuximab and dabrafenib for MSS BRAF V600E metastatic colorectal cancer

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

This trial will test whether combining the immunotherapies sintilimab and ipilimumab N01 with cetuximab and dabrafenib helps people with microsatellite-stable, BRAF V600E metastatic colorectal cancer live longer or have better tumor control.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: sintilimab, ipilimumab, cetuximab, chemotherapy, immunotherapy
• Locations: 4 sites (Beijing, Beijing Municipality and 3 other locations)
• Trial ID: NCT07506109 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase II trial testing a four-drug combination of sintilimab (anti-PD-1), ipilimumab N01 (anti-CTLA-4), cetuximab (EGFR inhibitor) and dabrafenib (BRAF inhibitor) in patients with MSS, BRAF V600E-mutated metastatic colorectal cancer. The rationale is that BRAF and EGFR blockade can induce DNA damage and raise tumor mutational burden, potentially making MSS tumors more responsive to immune checkpoint blockade. Eligible patients are adults with unresectable or metastatic colorectal adenocarcinoma that is MSS and BRAF V600E-mutant, with ECOG 0–1 and measurable disease, and no prior BRAF/EGFR/immune checkpoint therapy. The primary goals are to measure anti-tumor activity and safety of this combination at participating centers in China.

Who should consider this trial

Good fit: Adults (≥18) with unresectable or metastatic colorectal adenocarcinoma that is confirmed BRAF V600E-mutated and microsatellite-stable, ECOG performance status 0–1, measurable disease, adequate organ function, and no prior BRAF/MEK/ERK, EGFR, or immune checkpoint inhibitor therapy.

Not a fit: Patients who are MSI-high, lack a BRAF V600E mutation, have received prior BRAF/EGFR/immune checkpoint therapies, or have poor performance status or inadequate organ function are unlikely to benefit or to qualify.

Why it matters

Potential benefit: If successful, this combination could produce longer responses and improved survival for patients with BRAF V600E MSS metastatic colorectal cancer who currently have poor outcomes with standard treatments.

How similar studies have performed: Combinations of BRAF and EGFR inhibitors have shown clinical benefit in BRAF V600E mCRC (for example the BEACON regimen), and preclinical and early clinical data support adding PD-1/CTLA-4 blockade for MSS tumors, but the full four-drug regimen remains novel.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality and 3 other locations

• Peking union medical college hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• West China Hospital Sichuan University — Chengdu, Sichuan, China (Not_yet_recruiting)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Conditions BRAF V600E; Colorectal Cancer; Sintilimab; MSS; Cetuximab; Dabrafenib; Ipilimumab N01