KO-2806 Monotherapy and Combination Therapies in Advanced Solid Tumors

Inclusion Criteria:

1. At least 18 years of age.
2. Histologically or cytologically confirmed advanced solid tumors

1. Arm #1 (Monotherapy): HRAS-mutant and/or amplified tumors (any solid tumor type); HRAS overexpression (only for HNSCC tumors); KRAS and/or NRAS, and/or HRAS-mutant and/or amplified NSCLC or CRC; KRAS-mutant and/or amplified PDAC
2. Arm #2 (Combination): Must have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype
3. Arm #3 (Combination): Must have KRAS G12C-mutant locally advanced or metastatic NSCLC and have received at least 1 prior systemic therapy for advanced or metastatic NSCLC
4. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
5. Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks.
6. Acceptable liver, renal, endocrine, and hematologic function.

* Other protocol-defined inclusion criteria may apply.

Exclusion Criteria:

1. Ongoing treatment with certain anticancer agents.
2. Prior treatment with an FTI or HRAS inhibitor.
3. Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery.
4. Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases.
5. Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent.
6. Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions).
7. Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
8. Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs.
9. Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebro-vascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure.
10. Other invasive malignancy within 2 years.

* Other protocol-defined exclusion criteria may apply.