Metformin Combined With Chemotherapy and/or Immunotherapy in Solid Malignancies

Inclusion criteria

• Have histologically confirmed advanced solid tumor and are considered a suitable candidate for chemotherapy and/or immunotherapy or both
• Are a male or female participant aged ≥ 18 years
• Have provided a signed, written informed consent form
• Have measurable disease per RECIST v1.1
• Have adequate hematologic, renal, liver, and coagulation function as defined by the following:

• Hemoglobin ≥ 8 g/dL if determined suitable by the investigator for the selected chemotherapy and/or immunotherapy regimen for the particular patient
• Absolute neutrophil count (ANC) > 1500/mm3
• Platelets > 75,000/mm3 if determined suitable by the investigator for the selected chemotherapy and /or immunotherapy regimen for the particular patient
• Estimated Glomerular Filtration Rate (eGFR) > 45 mL/min/1.73 m2 (as described by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 equation)
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Participants with known Gilbert's syndrome who have total bilirubin level ≤ 3 x ULN may be enrolled if deemed suitable for a particular patient by the investigator for the selected chemotherapy and/or immunotherapy regimen.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN. For participants with hepatic metastases, AST and ALT ≤ 5 x ULN.
• Alkaline phosphatase (ALP) < 2.5 x ULN. For participants with hepatic and/or bone metastases ≤ 5 x ULN
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, and suitable for chemotherapy/IO recommended by the investigator.
• Participants who have experienced expected toxicity from Cycle 1 of anticancer therapy which is unlikely to recover to grade 1 or better prior to Cycle 2 (e.g., anemia, alopecia, vitiligo, endocrine dysfunction associated with IO) and may otherwise not impact the eligibility will be allowed.
• Women of child-bearing potential must agree to avoid becoming pregnant and male participants should avoid impregnating a female partner or donating sperm starting at initiation of treatment up until at least 90 days after the last dose of study drug.
• Have an estimated life expectancy of at least 12 weeks

Exclusion criteria

• Patients who have or are any of the following exclusion criteria are not eligible for participation in the study.
• Patients with uncontrolled diabetes
• Patients who have received metformin must be at least five half-lives beyond such treatment (four weeks) and must not be taking metformin at the time of enrollment.
• Patients with a known hypersensitivity to metformin, its excipients, its analogs, or any of its components
• Patients on other antidiabetic medicines are eligible as long as adding metformin will not be contraindicated
• Patients with an inability to tolerate oral medications
• Women who are pregnant or lactating
• Patients with clinically significant intercurrent disease including, but not limited to:

• New York Heart Association Class III or IV heart failure
• Myocardial infarction, unstable angina, or stroke ≤ 3 months prior to Cycle 1 Day 1
• Uncontrolled arrhythmia
• Clinically significant active infection requiring IV antibiotic, antiviral, or antifungal medications
• Patients with other current medical or other conditions that, in the opinion of the investigator, may confound study interpretation or prevent completion of study procedures and follow-up examinations
• Patients with an unwillingness or inability to comply with the study procedures required in this protocol
• Patients using an investigational agent within four weeks of study entry
• Patients with uncontrolled metabolic disorders or primary or secondary effects of cancer that induce a high medical risk