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
Single group
Balstilimab
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Botensilimab
Biological/VaccineGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT scan
Dietary Intervention
Other interventionUndergo FMD
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Vitamin C
Dietary supplementGiven IV
Proportion of patients who adhere to the fast mimicking diet
Adherence will be defined as the percentage of patients who adhere to the fasting-mimicking diet ≥ 75% of the designated days and receive all doses of study drugs for at least any 2 cycles of therapy during the course of the study. Adherence will be reported overall and by cycle started.
Incidence of adverse events (AEs)
The frequency and severity of treatment-related events will be assessed using Common Terminology Criteria for Adverse Events version 5.0. Descriptive statistics will be used to summarize AEs including counts for categorical measures and means for continuous measures. Incidence of AEs will be reported overall and by cycle started.
Overall response rate (ORR)
ORR will be evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm; Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Progression-free survival (PFS)
Measured from start of treatment to the date of event defined as the first documented progression or death due to any cause. PFS Progression will be evaluated using RECIST v1.1. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
Overall survival (OS)
Measured from start of treatment until death from any cause. Patients who are still alive at the time of the analysis, or who have become lost to follow-up or withdrawn consent will be censored at their last date known to be alive.
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University of Southern California
Lead sponsor
National Cancer Institute (NCI)
Collaborator
