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 usingeither tumor tissue or ctDNA.

• Histologically confirmed malignant solid tumor with locally advanced and/ormetastatic 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 platinumbased chemotherapy regimen either concurrently or sequentially

• Part 2 (Cohort B - CRC): Received at least 1 line of systemic therapy that includesthe combination of fluoropyrimidine-based chemotherapy (in combination withoxaliplatin and/or irinotecan) and either a vascular endothelial growthfactor-targeting monoclonal antibody or an anti-epidermal growth factor receptormonoclonal antibody (if RAS wild type). Participants with MSI-H/dMMR CRC must alsohave 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 leptomeningealdisease.

• Part 2 only: Prior treatment with an approved or investigational agent targetingKRASG12C.

• 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 studytreatment.

• Participation in another interventional clinical study.

• History or evidence of interstitial lung disease, including noninfectiouspneumonitis.

• Presence of gastrointestinal condition that may affect drug absorption.

• Active autoimmune disease requiring systemic treatment, including corticosteroidsexceeding a daily dose of 10 mg of prednisone or equivalent.

• Diagnosis of immunodeficiency or receiving chronic systemic steroid therapyexceeding 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 treatmentperiod.

• 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.