Metformin in Combination with Chemotherapy and/or Immunotherapy for the Treatment of Advanced Solid Tumors

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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1
• 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/mm^3 * Patients with Duffy-null associated neutrophil count (SNP rs2814778 at chromosome 1q23.2) must have an ANC > 1250/mm^3 if determined suitable by the investigator for the selected chemotherapy and/or immunotherapy regimen for the particular patient
• Platelets > 75,000/mm^3 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 m^2 (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
• 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 * Female participants must meet one of the following: ** Surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) ** Post-menopausal, defined as no menses for at least 12 months prior to the screening visit without alternative medical causation ** Agree to practice true abstinence from sexual intercourse when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence methods such as calendar, ovulation, symptothermal, or post ovulation tracking are not acceptable ** Not in a sexual relationship in which they may become pregnant (i.e., same-sex relationship) ** If they are of childbearing potential, agree to use at least one highly effective AND at least one additional method of contraception. Withdrawal is not an acceptable contraceptive method * Male participants must meet one of the following: ** In a sexual relationship with a post-menopausal or surgically sterile female (see above definitions) ** Agree to practice true abstinence from sexual intercourse with a female of child-bearing potential starting at initiation of therapy up until at 30 days after the last study drug dose ** Not in a sexual relationship in which their partner may become pregnant (i.e., same-sex relationship) ** In a sexual relationship with a woman of child-bearing potential and agree to use at least one highly effective AND at least one additional method of contraception. Withdrawal is not an acceptable contraceptive method * Highly effective methods ** Intrauterine device (IUD) ** Hormonal therapy (birth control pills, injection, implants) ** Tubal ligation ** Vasectomy * Additional methods of contraception ** Male OR female condoms (should not be used together) used with a spermicide ** Diaphragm ** Cervical cap
• Have an estimated life expectancy of at least 12 weeks

Exclusion Criteria

• Patients with uncontrolled diabetes (glycosylated hemoglobin [HbA1c] ≥ 9.0%)
• 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