Nivolumab With or Without Ipilimumab in Advanced Metastatic Cancer

Inclusion Criteria

• Participant must be ≥ 18 years of age inclusive, at the time of signing the informed consent.
• Male or female participants of child-producing potential must agree to use contraception or avoidance of pregnancy measures during the study and for 7 and 5 months, respectively, after the last dose.
• Females of childbearing potential must have a negative serum or urine pregnancy test.
• Histologically or cytologically confirmed cancer that is metastatic, unresectable, or recurrent and are responsive to immunomodulation (ie, with US Prescribing Information [USPI]). Participants who have failed or refused available approved treatment options are eligible to participate.
• Participants who have received prior immunotherapy, including prior anti-PD-1 or anti-PD-L1 therapies, will be allowed to participate in this study.
• Participants who received prior anti-PD-1 or anti-PD-L1 may participate only if their prior anti-PD-1 or anti-PD-L1 monotherapy or combination therapy were NOT the last treatment prior to participation on this study.
• Participants who had prior immunotherapies and experienced Grade 1-2 immune-related adverse event (irAE) must have documentation that their irAEs are ≤ Grade 1 or baseline using current Common Terminology Criteria for Adverse Events v5.0 (CTCAE v5.0) and participants must be off steroid therapy and/or other immunosuppressive therapy, as treatment for irAEs, for ≥ 14 days from Cycle 1, Day 1.
• Participants who experienced Grade 3 irAEs consisting of laboratory abnormalities that were asymptomatic and have now resolved to ≤ Grade 1 or baseline and participants who have been off steroid and/or other immunosuppressive therapy, as treatment for irAEs, for ≥ 30 days from Cycle 1, Day 1.
• Concurrent malignancies are permitted if any one of the following applies:
• Previously treated malignancy for which all treatment of that malignancy was completed at least 2 years before enrollment and no evidence of disease exists, or
• With agreement from the Sponsor and Principal Investigator (PI), participants who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment are eligible to participate if the risk of the prior malignancy interfering with either safety or efficacy endpoints is very low, or
• With agreement from the Sponsor and PI, other malignancies may be permitted if the risk of the prior malignancy interfering with either safety or efficacy end points is very low.
• Provide newly obtained core needle or incisional biopsy of a tumor lesion not previously irradiated. Fine needle aspiration is not acceptable.

a. Biopsies should be obtained from sites that do not pose significant risk to the participant based on the tumor site and the procedure used. Biopsy sites/procedures including, but not limited to, the brain, open lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel would be considered to pose a significant risk to the participant. Procedures to areas that are deemed by the Investigator to be of non-significant risk based on individual clinical scenarios will be permitted.

• Measurable disease as defined by RECIST v1.1.

a. Participants who do not have measurable disease by RECIST criteria but whose disease can be objectively measured through tumor markers or another disease specific standard are considered eligible.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN).
• Participants who have liver lesions may be eligible if they have AST and ALT

≤ 3.0 x ULN.

• Participants with hepatocellular carcinoma (HCC) may be eligible provided they have AST and ALT that are ≤ 5.0 x ULN.
• Hemoglobin ≥ 9 g/dL.
• Total bilirubin ≤ 1.5 × ULN. Participants with liver lesions who do not have HCC and who have a total bilirubin 10 mg/day prednisone or