Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation has been identified as a driver oncogenic mutation in several solid tumors (eg, non-small cell lung cancer [NSCLC], colorectal cancer [CRC]). Development of therapies targeting KRAS^G12C has been unsuccessful. AMG 510 is a specific and irreversible small molecule inhibitor of KRAS^G12C. A first-in-human clinical trial of AMG 510 monotherapy in patients with KRAS p.G12C mutant solid tumors is currently ongoing. AMG 510 in combination with additional anticancer therapies may lead to enhanced antitumor efficacy. This study is a master protocol designed to evaluate multiple investigational regimens of AMG 510 in patients with KRAS p.G12C mutant solid tumors. Here, we present two combination cohorts of AMG 510 with a mitogen-activated protein kinase kinase (MEK) inhibitor and an investigational anti-programmed cell death protein-1 (PD-1) therapy, respectively. Additional combination cohorts will be presented at the meeting. Methods: This is a phase 1b, open-label study evaluating AMG 510 in combination with a MEK inhibitor or an investigational anti-PD-1 therapy in pts with KRAS p.G12C mutant solid tumors. The dose exploration phase (part 1; n=20) will evaluate the safety and tolerability of AMG 510 in combination with the MEK inhibitor or anti-PD-1 therapy; this will be followed by a dose expansion phase (part 2; n=40) to verify the safety and tolerability profile of AMG 510 combination therapies and assess antitumor efficacy. Key eligibility criteria include locally-advanced or metastatic malignancy with KRAS p.G12C mutation identified through molecular testing and at least one or multiple lines of prior systemic therapy (eg, ≥2 for advanced/metastatic colorectal cancer). Primary endpoints include dose-limiting toxicities, treatment-emergent or -related adverse events. Secondary endpoints include pharmacokinetic parameters of combination regimens, disease control rate, duration of response, progression-free survival, and duration of stable disease (measured by computed tomography or magnetic resonance imaging and assessed per RECIST 1.1). The study began enrolling pts in December 2019 and is ongoing. For more information, please contact Amgen Medical Information: medinfo@amgen.com. Clinical trial information: NCT04185883.