A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

Inclusion Criteria:

* KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA.
* Histologically confirmed malignant solid tumor with locally advanced and/or metastatic disease.

  * Only participants with NSCLC will be enrolled into Part 2 Cohort A.
  * Only participants with CRC will be enrolled into Part 2 Cohort B.
* Part 1: Disease progression on or after at least 1 prior systemic treatment.
* Part 2 (Cohort A - NSCLC): Received an anti-PD-(L)1-containing regimen and platinum based chemotherapy regimen either concurrently or sequentially
* Part 2 (Cohort B - CRC): Received at least 1 line of systemic therapy that includes the combination of fluoropyrimidine-based chemotherapy (in combination with oxaliplatin and/or irinotecan) and either a vascular endothelial growth factor-targeting monoclonal antibody or an anti-epidermal growth factor receptor monoclonal antibody (if RAS wild type). Participants with MSI-H/dMMR CRC must also have received a prior immune checkpoint inhibitor approved for this indication.
* Measurable disease according to RECIST v1.1.
* Eastern Cooperative Oncology Group performance status of 0 or 1.
* Estimated life expectancy \> 3 months.
* Willingness to avoid pregnancy.

Exclusion Criteria:

* Known additional malignancy that is progressing or requires active treatment.
* Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease.
* Part 2 only: Prior treatment with an approved or investigational agent targeting KRASG12C.
* Toxicity from prior therapy that has not recovered to protocol-defined limits.
* Received thoracic radiation of \> 30 Gy within 6 months of the first dose of study treatment.
* Participation in another interventional clinical study.
* History or evidence of interstitial lung disease, including noninfectious pneumonitis.
* Presence of gastrointestinal condition that may affect drug absorption.
* Active autoimmune disease requiring systemic treatment, including corticosteroids exceeding a daily dose of 10 mg of prednisone or equivalent.
* Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy exceeding a daily dose of 10 mg of prednisone or equivalent.
* Active infection requiring systemic therapy.
* History of organ transplantation, including allogeneic stem cell transplantation.
* Receipt of systemic antibiotics within 28 days of the first dose of study treatment.
* Probiotic usage is prohibited during screening and throughout the study treatment period.
* Received a live vaccine within 28 days of the planned start of study drug.
* Laboratory values outside the Protocol-defined ranges.

Other protocol-defined Inclusion/Exclusion Criteria may apply.