A Trial of Pembrolizumab and Metformin Versus Pembrolizumab Alone in Advanced Melanoma

Exclusion Criteria

• •Has a current confirmed diagnosis of type 1 diabetes or type 2 diabetes that has been diagnosed by an HbA1c ≥6.5, or is on any hypoglycemic medications (insulin, metformin, etc). Patients with a screening HbA1c 6.5-7.0 may be included after discussion with the principal investigator. Patients currently on metformin will be excluded.
• •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• •Has a known history of active TB (Bacillus Tuberculosis).
• •Hypersensitivity to pembrolizumab or any of its excipients.
• •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 (this excludes patients on anti-PD1) or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least two weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• •Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxineor physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• •Has an active infection requiring systemic IV antibiotic therapy.
• •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• •Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• •Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• •Has a known history of or is positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (hepatitis C virus \[HCV\] RNA \[qualitative\] is detected). Note: Without known history, testing only needs to be performed if there is clinical suspicion for Hepatitis B or C.
• •Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.