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.