Phase I/II Trial of Encorafenib, Cetuximab, and Nivolumab in Microsatellite Stable BRAFV600E Metastatic Colorectal Cancer (BMS-MDACC CA209-8P6/ARRAY IST-818-101X)
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.
• Provision of signed Informed Consent prior to any screening procedures being performed. A translator may be used for patients who do not speak or read English.
• Age ≥ 18 years at the time of informed consent.
• Histologically (or cytologically) confirmed diagnosis of adenocarcinoma of the colon or rectum, with clinical confirmation of unresectable and/or metastatic disease that is measurable according to RECIST1.1 criteria.
• Confirmation of BRAFV600E tumor as detected by a CLIA-certified laboratory.
• Confirmation of MSS status in a CLIA-certified laboratory.
• Cohort A only: Prior treatment with at least one, but no more than two, systemic chemotherapy regimen(s) for mCRC, or recurrence/progression with development of unresectable or metastatic disease within 6 months of adjuvant chemotherapy for resected colorectal cancer.
• Cohort B only: prior treatment with a BRAF, anti-EGFR, MEK, or ERK targeted therapy for treatment of colorectal cancer
• ECOG performance status \< 1
• Adequate bone marrow, organ function and laboratory parameters:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L,
• Hemoglobin (Hgb) ≥ 9 g/dL with or without transfusions,
• Platelets (PLT) ≥ 100 x 109/L without transfusions,
• AST and/or ALT ≤ 2.5 × upper limit of normal (ULN). If liver metastases are present, then it is acceptable for AST level ≤ 5.0 × ULN, and an ALT level ≤ 5.0 × ULN.
• Total bilirubin ≤ 1.5 × ULN and \< 2 mg/dL Note: Patients who have a total bilirubin level \> 1.5 x ULN will be allowed if their indirect bilirubin level is ≤ 1.5 x ULN
• Serum Creatinine ≤ 1.5 x ULN, or calculated creatinine clearance (determined as per Cockcroft-Gault) ≥ 50mL/min at screening;
• QTc interval ≤ 480 ms (preferably the mean from triplicate ECGs) ;
• Able to take oral medications;
• Female patients are either postmenopausal for at least 1 year, are surgically sterile for at least 6 weeks, or must agree to take appropriate precautions to avoid pregnancy from screening through follow-up if of childbearing potential Note: Permitted contraception methods listed in Section 8.2 should be communicated to the patients and their understanding confirmed. For all females, the pregnancy test result must be negative within 24 hours of starting treatment with nivolumab. Males must agree to take appropriate precautions to avoid fathering a child from screening through 100 days following the end of therapy.