Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Adenocarcinoma

Colorectal Neoplasms

Rectal Neoplasms

Colonic Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Herbal and Botanical

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Cola

Participants in Phase 1 receive encorafenib PO QD on days 1-28, binimetinib PO BID on days 1-28, and nivolumab IV on day 1. Cycles repeat every 28 days for a maximum of 24 cycles of treatment in the absence of disease progression or unacceptable toxicity.

The study was terminated before Phase II was initiated. The study did not open Phase II for enrollment.

Binimetinib

Encorafenib

Questionnaire Administration

Chloe E Atreya, MD, PhD

This phase I/II trial studies the side effects and how well encorafenib, binimetinib, and nivolumab work in treating patients with microsatellite stable, BRAFV600E gene-mutated colorectal cancer that has spread to other places in the body (metastatic). Encorafenib and binimetinib 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, binimetinib, and nivolumab may work better in treating patients with colorectal cancer compared to standard treatments.

This was intended to be a phase I/II study of Encorafenib, Binimetinib, and Nivolumab for treating participants with Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer. The study was terminated before Phase II was initiated. The study did not open Phase II for enrollment.

PRIMARY OBJECTIVES:

I. To describe overall response rate (ORR) upon treatment with encorafenib, binimetinib, and nivolumab in patients with BRAFV600E, microsatellite stable (MSS) metastatic colorectal cancer (mCRC).

II. To determine the safety and tolerability of nivolumab, encorafenib, and binimetinib in patients with BRAFV600E, MSS mCRC.

SECONDARY OBJECTIVES:

I. To estimate median progression-free survival (PFS) upon treatment with encorafenib, binimetinib, and nivolumab.

II. To estimate median overall survival (OS) upon treatment with encorafenib, binimetinib, and nivolumab.

III. To estimate median time to response (TTR) upon treatment with encorafenib, binimetinib, and nivolumab.

IV. To estimate median duration of response (DoR) upon treatment with encorafenib, binimetinib, and nivolumab.

V. To estimate disease control rate (DCR) upon treatment with encorafenib, binimetinib, and nivolumab.

EXPLORATORY (CORRELATIVE) OBJECTIVES:

I. To assess genomic and immune changes upon treatment with encorafenib, binimetinib, and nivolumab in tumor tissue, blood and stool.

II. To correlate genomic and immune changes upon treatment with encorafenib, binimetinib, and nivolumab in tumor tissue, blood and stool with radiographic response.

III. To evaluate contrast-enhanced computed tomography (CT) imaging for disease burden that is not measurable by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and to correlate location and patterns of metastatic disease with clinical outcomes.

OUTLINE:

Participants in received encorafenib orally (PO) once daily (QD) on days 1-28, binimetinib PO twice daily (BID) on days 1-28, and nivolumab intravenously (IV) on day 1. Cycles repeat every 28 days for a maximum of 24 cycles of treatment. If disease progression or recurrence occurs, treatment may be resumed outside of the context of the clinical trial.

After completion of study treatment, patients are followed up at 30 and 100 days, then every 3 months thereafter.

Only participants in Phase 1 were enrolled.

Encorafenib, Binimetinib, and Nivolumab in Treating Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer

Phase I/II Trial of Encorafenib, Binimetinib, and Nivolumab in Microsatellite Stable BRAF V600E Metastatic Colorectal Cancer

Will be measured according to immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). The point estimate of the objective response rate (ORR) and its 95% confidence interval will be obtained.

Will be assessed in the following order of importance: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), and not evaluable. The point estimate of the ORR and its 95% confidence interval will be obtained

Will be graded according to the Common Terminology Criteria for Adverse Events version 5.0. Safety data will be tabulated.

Will be defined by irRECIST criteria for the evaluable population. Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until death or PD

Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until death occurs

Will be defined by irRECIST criteria. Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from start of treatment until time of response.

Will be estimated by Kaplan-Meier method and summarized with Kaplan-Meier curves and log rank test from first partial or CR to time of PD or death for subjects with a response

The proportion of patients with CR, PR, or SD defined by irRECIST criteria in the evaluable population. The point estimate of DCR and its 95% confidence interval will be obtained.

Spots Global Cancer Trial Database for microsatellite status (mss)