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

Plain English Summary

A Phase II Study of Sintilimab Combined With Ipilimumab N01, Cetuximab and Dabrafenib in Patients With Microsatellite-Stable, BRAF V600E-Mutated Metastatic Colorectal Cancer is a Phase 2 clinical trial sponsored by Tianjin Medical University Cancer Institute and Hospital studying BRAF V600E, Colorectal Cancer, Sintilimab, MSS (Microsatellite Stable), Cetuximab, Dabrafenib, Ipilimumab N01. This trial tests a new combination of four drugs (sintilimab, ipilimumab N01, cetuximab, and dabrafenib) to treat a specific type of advanced colorectal cancer. It is for patients with metastatic colorectal cancer that has a BRAF V600E mutation and is microsatellite stable (MSS). Participants will receive the combination therapy intravenously and orally. They will have regular study visits for assessments and monitoring. Standard chemotherapy is the current treatment for this condition, but this trial explores a novel approach. The trial aims to enroll 49 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18 or older with confirmed colorectal cancer that has spread and has specific genetic markers (BRAF V600E mutation and MSS). Patients who have not previously received treatment with BRAF/MEK/ERK inhibitors, EGFR inhibitors, or immune checkpoint inhibitors. Patients must have measurable disease and be in good general health with adequate organ function. Individuals with other serious medical conditions, pregnant or breastfeeding women, or those with multiple primary cancers (with some exceptions) cannot participate. This trial is studying BRAF V600E, Colorectal Cancer, Sintilimab, MSS (Microsatellite Stable), Cetuximab, Dabrafenib, Ipilimumab N01, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients live without their cancer getting worse, which means it aims to see if the new drug combination can control the cancer for a longer period. The specific primary outcome measures are: Progression-Free Survival (PFS) (up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical unmet need for patients with BRAF V600E-mutated metastatic colorectal cancer, a group with a poor prognosis that often doesn't respond well to current standard treatmen Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets BRAF V600E, Colorectal Cancer, Sintilimab, MSS (Microsatellite Stable), Cetuximab, Dabrafenib, Ipilimumab N01, where improved treatment options are needed.

Investor Insight

This trial targets a specific, aggressive subtype of colorectal cancer, potentially opening a new treatment avenue and indicating a growing interest in personalized medicine approaches for this diseas Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if your cancer has a BRAF V600E mutation and is microsatellite stable (MSS). Understand that participation involves receiving a combination of four drugs and attending regular clinic visits for tests and check-ups. Be prepared for potential side effects and the need for close monitoring throughout the study. This trial is currently recruiting participants. The trial is being conducted at 4 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 49 participants

Interventions

• 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.
• DRUG: Sintilimab — 2mg/kg ivd, q3w
• DRUG: Cetuximab — 500mg/m2 ivd，q2w
• DRUG: Dabrafenib — 150mg po bid

Primary Outcomes

• Progression-Free Survival (PFS) (up to 2 years)

Secondary Outcomes

• 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)

Full 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.

Trial Locations

• 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

Frequently Asked Questions

Related Conditions

• Colorectal Cancer
• Metastatic Cancer
• BRAF V600E Mutation
• Microsatellite Stable Colorectal Cancer
• Gastrointestinal Cancers
• Oncology
• Cancer Immunotherapy
• Targeted Cancer Therapy
• Personalized Medicine
• Drug Combinations

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