* 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.
You may not be if
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.
Clareo Health | A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation
