A Phase II Clinical Trial of Anti-PD-1 mAb Therapy Alone or With Metabolic Modulators to Reverse Tumor Hypoxia and Immune Dysfunction in Solid Tumor Malignancies

Inclusion Criteria: 1. Histologically or cytologically confirmed advanced melanoma, renal cell carcinoma, NSCLC, HCC (Child Pugh Class A only), MSI-High solid tumors, Urothelial Cancer, GE junction/Gastric Adenocarcinoma, or HNSCC for which current standard of care treatment for their stage of disease would be with Pembrolizumab or Nivolumab monotherapy. 2. Accessible tumor for pretreatment (baseline) and post treatment biopsy. Tumor must be accessible for core or surgical biopsy (excisional/incisional), FNA is not adequate 3. Age ≥ 18 years 4. Have at least one measurable area of disease (Target Lesion) based on RECIST 1.1. 5. ECOG performance status 0-2 6. Patients must have normal organ and marrow function as defined below: absolute neutrophil count ≥1,500/mcL platelets ≥100,000/mcL total bilirubin ≤ institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN Creatinine clearance ≥40 mL/min/1.73 m2 7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 7 days prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 8. Female subjects of childbearing potential should be willing to use one methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Women of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. 9. Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. 10. Ability to understand and the willingness to sign a written informed consent document 11. If known to have prior brain metastases, must not have evidence of active (enlarging and/or symptomatic lesions) brain disease on MRI/CT evaluation. 12. A type II DM patient who does not currently require prescription medication for diabetes treatment and has not received metformin, insulin, sulfonylureas or thiazolidinediones within 60 days of the start of study treatment can be enrolled on the study. Exclusion Criteria: 1. Treatment with prior anti-PD-1 or anti-PD-L1 mAb therapy 2. Patients with type I DM or any patient who has received metformin, insulin, sulfonylureas, or thiazolidinediones within 60 days of start of study treatment for any reason. 3. Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study must be informed of the risks to any sexual partner of childbearing potential and should practice an effective method of birth control. 4. All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. 5. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study. 6. History of uncontrolled cardiac disease (e.g., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months) 7. Symptomatic heart failure or New York Heart Association Class III or IV heart failure 8. Psychiatric illness or other social issues limiting compliance 9. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis. 10. Treatment with a non-approved or investigational drug within 14 days prior to Day 1 of study treatment. 11. Prior malignancy within 2 years with the exception of adequately treated basal cell or squamous cell skin cancer, carcinoma of the cervix or prostate cancer. 12. 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. 13. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Per Medical History Review 14. Hypersensitivity to metformin, rosiglitazone, pembrolizumab or nivolumab 15. Unable to take in pills either orally or via feeding tube 16. History of acidosis of any type or habitual intake of 5 or more alcoholic beverages a day. 17. Patients that require active treatment with Rifampin or Gemfibrozil for other medical conditions.