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.
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.
Patients receive 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.
| Condition | Stage III Colorectal Cancer, Stage IIIA Rectal Cancer, Stage IIIB Rectal Cancer, Stage IIIC Rectal Cancer, Stage IV Colon Cancer, Stage IV Rectal Cancer, Stage IVA Colon Cancer, Stage IVA Rectal Cancer, Stage IVB Colon Cancer, Stage IV Colorectal Cancer, Stage IIIA Colon Cancer, Stage IIIB Colon Cancer, Stage IIIC Colon Cancer, Stage IVB Rectal Cancer, Metastatic Colon Cancer, Stage III Colon Cancer, Stage III Rectal Cancer, Stage IIIA Colorectal Cancer, Stage IIIB Colorectal Cancer, Stage IIIC Colorectal Cancer, Stage IVA Colorectal Cancer, Stage IVB Colorectal Cancer, Metastatic Colorectal Adenocarcinoma, Metastatic Colon Adenocarcinoma, Metastatic Microsatellite Stable Colorectal Carcinoma, Metastatic Rectal Adenocarcinoma, Stage IVC Colorectal Cancer, Stage IVC Colon Cancer, Stage IVC Rectal Cancer |
|---|---|
| Treatment | questionnaire administration, Nivolumab, Binimetinib, Encorafenib |
| Clinical Study Identifier | NCT04044430 |
| Sponsor | University of California, San Francisco |
| Last Modified on | 21 March 2021 |
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