This phase Ib trial tests the safety, side effects, and effectiveness of botensilimab, and balstilimab in combination with a fasting mimicking diet and high dose vitamin C in treating patients with KRAS-mutant metastatic colorectal cancer. Botensilimab and balstilimab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. KRAS is protein found on some tumor cells that is involved in the growth of tumor cells. KRAS mutant cells have been found to be more sensitive to vitamin C induced growth suppression in the presence of low-sugar (glucose). A fasting mimicking diet, a plant-based, calorie reduced, low-sugar diet alternating with refeeding periods, may positively change the way the body responds to cancer treatment. Vitamin C is a nutrient that the body needs in small amounts to function and stay healthy. It is an antioxidant that that can help prevent cell damage and may block growth and spread of tumor cells. Botensilimab and balstilimab in combination with a fasting mimicking diet and high dose vitamin C may be safe, tolerable and effective in treating patients with KRAS-mutant metastatic colorectal cancer.
Histologically or cytologically confirmed microsatellite stable (MSS) metastatic colorectal adenocarcinoma with any KRAS mutation (as determined by a Clinical Laboratory Improvement Act [CLIA]-certified lab), including metastases to liver, lung, etc.
Disease progression, intolerance or contraindication to a fluoropyrimidine, oxaliplatin, irinotecan
≥ 18 years of age
Performance status Eastern Cooperative Oncology Group (ECOG) 0-1
Patients with a current diagnosis of diabetes mellitus are not eligible for this study.
Patients taking medications that cannot be safely stopped during the fasting periods or which may not be safely taken without food are not eligible for this study
Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks prior to first dose of study drug. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease, with approval from the principal investigator
History of syncope with caloric restriction or another medical comorbidity which would make fasting potentially dangerous
University of Southern California
Lead sponsor
National Cancer Institute (NCI)
Collaborator