KO-2806 for Advanced Solid Tumors

Inclusion Criteria: * At least 18 years of age. * Histologically or cytologically confirmed advanced solid tumors * Arm #1 (KO-2806 monotherapy): Patients who have progressed on, or are refractory to, standard of care (SOC) treatments with advanced solid tumors, specifically: 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 * Arm #2 (Combination): Patients who have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic RCC with predominantly clear cell subtype; non-clear cell RCC patients who are either treatment-naïve or have received any prior systemic treatment for locally advanced and metastatic RCC. * Arm #3 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC, CRC, or PDAC. * Arm #4 (Combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #5 (Cabozantinib monotherapy): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #6 (Cabozantinib rollover to combination): Patients must be cabozantinib-naïve and have received at least 1 prior systemic therapy with IO-based treatment for locally advanced or metastatic ccRCC, but no more than 3 prior systemic anticancer therapies. * Arm #7 (Combination): Patients who have received at least 1 prior systemic therapy including available approved SOC treatments for KRAS G12C-mutant locally advanced or metastatic NSCLC * Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Karnofsky Performance Status of 70 or higher with no clinically significant deterioration over the previous 2 weeks. * Acceptable liver, renal, endocrine, and hematologic function. * Other protocol-defined inclusion criteria may apply. Exclusion Criteria: * Any use of anticancer therapy within 14 days or 5 half-lives (whichever is shorter) of Cycle 1 Day 1. * Prior treatment with an FTI or HRAS inhibitor. * Major surgery, other than local procedures, within 28 days prior to Cycle 1 Day 1, without complete recovery. * Spinal cord compression, leptomeningeal disease, or clinically active CNS metastases. * Toxicity (excluding alopecia) from prior therapy that has not been completely resolved to baseline at the time of consent. * Active or prior documented autoimmune or inflammatory disorders within the past 5 years prior to Cycle 1 Day 1 (with exceptions). * Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy. * Inability to swallow, impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the trial drugs. * Inadequate cardiac and/or vascular function, including receipt of treatment for unstable angina, myocardial infarction, and/or cerebrovascular attack within the prior 6 months, mean QTcF ≥470 ms, or Class II or greater congestive heart failure. * Other invasive malignancy within 2 years. * Other protocol-defined exclusion criteria may apply.