Interventional Study of INCB 99280 With Ipilimumab in Participants With Select Solid Tumors

Inclusion Criteria: * Prior systemic therapy, diagnoses and disease setting as follows: * For Part 1 (dose escalation), and no history of treatment with anti-CTLA-4 or anti-PD-(L)1 therapy and one of the following, * Unresectable or metastatic cutaneous melanoma, or * Unresectable of metastatic Child-Pugh Class A NDD not eligible for surgical and/or locoregional therapy, or * Intermediate or poor-risk advanced clear cell RCC, or * MSI-H or dMMR metastatic CRC and able to provide fresh or archival tumor tissue for central confirmation of MSI-H or dMMR. * For Part 2 (dose expansion), IO treatment -naïve, e.g., no prior receipt of an anti PD-1, anti-PD-L1 or PD-L1, anti-CTLA-4, GITR, LAG3, TIM3, OX-40, IL-2, 4-1BB or other immune modulator, and have not received prior systemic therapy and one of the following, * Unresectable or metastatic Child-Pugh Class A HCC not eligible for surgical and/or locoregional therapy, or * Intermediate - or poor-risk advanced clear cell RCC. * ECOG performance score of 0 or 1. * Life expectancy \> 3 months, in the opinion of the investigator. * Histologically confirmed solid tumors with measurable disease per RECIST v1.1. * Exception: HCC may be diagnoses based on cross-sectional multiphasic imagining using the AASLD criteria. * Willingness to avoid pregnancy or fathering children. Exclusion Criteria: * Known history of an additional malignancy. * Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease. * Toxicity from prior therapy that has not recovered. * Received thoracic radiation within 6 months of the first dose of study treatment. * Participation in another interventional clinical study while receiving INCB099280. * Impaired cardiac function of clinically significant cardiac disease. * History of evidence of interstitial lung disease including non-infections pneumonitis. * Presence of gastrointestinal condition that may affect drug absorption * Any autoimmune disease requiring systemic treatment in the past 5 years. * Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent * Active infection requiring systemic therapy. * History of organ transplantation, including allogeneic stem cell transplantation. * Receipt of system antibiotics within 28 days of first dose of study treatment. * Probiotic usage is prohibited during the screening and throughout the study treatment period. * Received a live vaccine within 28 days of planned start of study drug. * Laboratory values outside the Protocol-defined ranges. Other protocol-defined Inclusion/Exclusion Criteria may apply.