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.