A Phase Ib Study of Botensilimab Plus Balstilimab and Fasting-Mimicking Diet (FMD) Plus Vitamin C in Patients With KRAS-Mutant Metastatic Colorectal Cancer

Inclusion Criteria: * 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 Exclusion Criteria: * Patients with a current diagnosis of diabetes mellitus are not eligible for this study. Note: Patients with pre-diabetes or previous diabetes or glucose intolerance and who are currently not taking any diabetes medications are eligible * 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 * Current use of oral vitamin C supplements * Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 3 weeks of first dose of current study drug * Expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent, radiation therapy, and/or surgical resection) * History of anti-PD1 or anti-CTLA4 therapy * Unresolved toxicity ≥ CTCAE grade 2 except for neuropathy, alopecia * Untreated brain or leptomeningeal metastases or previously treated CNS metastases with any of the following: residual neurologic deficit; history of seizures; ongoing requirement of steroids, exceeding prednisone 10 mg daily dose * Patients who have uncontrolled or severe hyponatremia, hypernatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalemia, hyperkalemia, hypomagnesemia, or hypermagnesemia * Patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency, hereditary spherocytosis, or other conditions predisposing patient to hemolysis * Patients who have a history of oxalate renal calculi * Major surgery within 4 weeks of first dose of immunotherapy * Known severe (grade ≥ 3) hypersensitivity reactions to fully human monoclonal antibodies, antibody, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with steroids; or has a history of interstitial lung disease, any history of anaphylaxis, or uncontrolled asthma * Evidence of bleeding diathesis or clinically significant coagulopathy * Receiving systemic corticosteroid therapy 1 week prior to the first dose of study drug or receiving any other form of systemic immunosuppressive medication. Note: Corticosteroid use as a premedication for IV contrast allergies/reactions is allowed. Patients who are receiving daily corticosteroid replacement therapy are also an exception to this rule. Daily prednisone at doses of ≤ 10 mg or equivalent hydrocortisone dose are examples of permitted replacement therapy. Use of inhaled or topical corticosteroid is permitted * Active or history of autoimmune disease that requires systemic treatment within 2 years of the start of study drug (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Patients with autoimmune conditions requiring hormone replacement therapy or topical treatments are eligible * Has had an allogeneic tissue/solid organ transplant, except for corneal transplants * Legally incapacitated or has limited legal capacity * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, active coronary artery disease, myocardial infarction or cerebrovascular accident within 6 months prior to study entry, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements