NCT04017650

Encorafenib, Cetuximab, and Nivolumab in Treating Patients With Microsatellite Stable, BRAFV600E Mutated Unresectable or Metastatic Colorectal Cancer

Phase I/II Trial of Encorafenib, Cetuximab, and Nivolumab in Microsatellite Stable BRAFV600E Metastatic Colorectal Cancer (BMS-MDACC CA209-8P6/ARRAY IST-818-101X)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/II trial studies the best dose and side effects of encorafenib, cetuximab, and nivolumab and how well they work together in treating patients with microsatellite stable, BRAFV600E gene mutated colorectal cancer that cannot be removed by surgery (unresectable) or has spread to other places in the body (metastatic). Encorafenib and cetuximab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.Giving encorafenib, cetuximab, and nivolumab may work better in treating patients with colorectal cancer compared to cetuximab alone.

Detailed description

PRIMARY OBJECTIVES: I. To describe overall response rate (ORR) upon treatment with encorafenib, cetuximab, and nivolumab. II. To determine the safety and tolerability of nivolumab, encorafenib, and cetuximab. SECONDARY OBJECTIVES: I. To estimate median progression-free survival (PFS) upon treatment with encorafenib, cetuximab, and nivolumab. II. To estimate median overall survival (OS) upon treatment with encorafenib, cetuximab, and nivolumab. III. To estimate median time to response (TTR) upon treatment with encorafenib, cetuximab, and nivolumab. IV. To estimate median duration of response (DOR) upon treatment with encorafenib, cetuximab, and nivolumab. V. To estimate disease control rate (DCR) upon treatment with encorafenib, cetuximab, and nivolumab. EXPLORATORY OBJECTIVES: I. To assess genomic and immune changes upon treatment with encorafenib, cetuximab, and nivolumab. II. To demonstrate feasibility of establishing humanized patient-derived xenograft models in matched patients with BRAFV600E metastatic colorectal cancer (mCRC). OUTLINE: This is a phase I, dose-escalation study followed by a phase II study. Patients receive encorafenib orally (PO) once daily (QD) on days 1-28, cetuximab intravenously (IV) over 1 hour on days 1 and 15, and nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 and 100 days, at 3 months, and then every 3 months thereafter.

Conditions

• BRAF NP_004324.2:p.V600E
• Metastatic Colon Adenocarcinoma
• Metastatic Microsatellite Stable Colorectal Carcinoma
• Metastatic Rectal Adenocarcinoma
• Progressive Disease
• Recurrent Colorectal Carcinoma
• Stage III Colorectal Cancer AJCC v8
• Stage IIIA Colorectal Cancer AJCC v8
• Stage IIIB Colorectal Cancer AJCC v8
• Stage IIIC Colorectal Cancer AJCC v8
• Stage IV Colorectal Cancer AJCC v8
• Stage IVA Colorectal Cancer AJCC v8
• Stage IVB Colorectal Cancer AJCC v8
• Stage IVC Colorectal Cancer AJCC v8
• Unresectable Colon Adenocarcinoma
• Unresectable Rectal Adenocarcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Cetuximab	Given IV
DRUG	Encorafenib	Given PO
BIOLOGICAL	Nivolumab	Given IV

Timeline

• Start date: 2019-06-14
• Primary completion: 2027-12-30
• Completion: 2027-12-30
• First posted: 2019-07-12
• Last updated: 2025-11-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study