This phase I trial studies the side effects and best dose of CA-4948 when given together with fluorouracil, leucovorin, oxaliplatin (FOLFOX) plus bevacizumab in treating patients with colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). CA-4948 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The chemotherapy drugs used in FOLFOX, fluorouracil and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin is used with fluorouracil to treat colorectal cancer. Bevacizumab is in a class of medications called anti-angiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to the tumor. This may slow the growth and spread of the tumor. Giving CA-4948 with FOLFOX plus bevacizumab may be safe, tolerable and/or effective in treating patients with metastatic colorectal cancer.
Patients must have histologically or cytologically confirmed colorectal adenocarcinoma
Patients must have unresectable or metastatic measurable disease on imaging for Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 determination within 28 days of registration
For patients enrolling to the expansion cohort, lesions must be amenable to research biopsy
Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CA-4948 (emavusertib) and FOLFOX in combination with bevacizumab in patients < 18 years of age, children are excluded from this study
Patients with high-frequency microsatellite instability (MSI-H) or deficient deoxyribonucleic acid (DNA) mismatch repair (dMMR) colorectal cancer at pre-enrollment screening
Patients with prolonged QT interval by Fridericia's correction formula (QTcF) (> 450ms) on screening electrocardiogram (ECG)
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia
Patients who are receiving any other investigational agents
National Cancer Institute (NCI)
Lead sponsor