A Phase Ib Study of Botensilimab Plus Balstilimab and Fasting-Mimicking Diet (FMD) Plus Vitamin C in Patients With KRAS-Mutant Metastatic Colorectal Cancer
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
• Estimated life expectancy ≥ 3 months
• Body mass index (BMI) ≥ 18.5
• Absolute neutrophil count ≥ 1,500/mcL
• Hemoglobin ≥ 8.0 g/dL
• Platelets ≥ 75,000/mcL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (for patients with Gilbert syndrome ≤ 3.0 x ULN)
• Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 x ULN
• Creatinine ≤ 1.5 x ULN
• Measurable disease as defined by RECIST 1.1
• No history of prior or current malignancy that requires active treatment
• Female patients of childbearing potential must be willing to use highly effective contraceptive measures starting with the Screening visit through 90 days after last dose of study treatment.
∙ Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
• Female patients of childbearing potential must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following:
‣ ≥ 45 years of age and has not had menses for \> 1 year
⁃ Amenorrheic for \> 2 years without a hysterectomy and/or oophorectomy and follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation
⁃ Status is post-hysterectomy, -oophorectomy, or -tubal ligation
• Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the trial starting with the Screening visit through 90 days after the last dose of study treatment is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
∙ Note: Abstinence is acceptable if this is the established and preferred contraception for the patient