PRIMARY OBJECTIVES:~I. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 (sotorasib) alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except colorectal carcinoma [CRC] and lung non-small cell carcinoma [NSCLC]) as measured by progression free survival (Cohort 1).~II. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by response rate (Cohort 2).~SECONDARY OBJECTIVES:~I. To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab as compared to AMG 510 alone in patients with advanced/metastatic KRAS G12C mutated solid tumors (except CRC and NSCLC) as measured by response rate, disease control rate, and overall survival (Cohort 1).~II, To evaluate the efficacy of the combination of AMG 510 (sotorasib) and panitumumab in patients with advanced/metastatic KRAS G12C mutated solid tumors that have progressed on a prior KRAS G12C inhibitor as measured by disease control rate, progression free survival (PFS), and overall survival (Cohort 2).~III. To further evaluate the safety and tolerability of the combination of AMG 510 (sotorasib) and panitumumab.~IV. To collect tissue and provide it to the ComboMATCH Registration Protocol to assess concordance between the diagnostic tumor mutation profile generated by the Designated Laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor-derived deoxyribonucleic acid (DNA) (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol.~CORRELATIVE EXPLORATORY OBJECTIVES:~I. To investigate the impact of concomitant mutations on the clinical benefit. II. To evaluate if changes in circulating tumor DNA (ctDNA) over time correlate with response to treatment.~III. To evaluate the relative mutant allele fraction of KRAS mutation as a predictor of clinical benefit.~IV. To evaluate if ERK 1/2 and PI3K pathway activation correlate with response and/or resistance.~OUTLINE: Patients are assigned to 1 of 2 cohorts.~COHORT I: Patients who have never received a KRAS G12C inhibitor randomized to arms A or B.~ARM A: Patients receive sotorasib orally (PO) and panitumumab intravenously (IV) on study. Patients also undergo collection of blood samples and a tumor biopsy before treatment and computed tomography (CT) or magnetic resonance imaging (MRI) at follow up.~ARM B: Patients receive sotorasib PO on study. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples and a tumor biopsy before treatment and CT or MRI at follow up.~COHORT II: Patients who have received a KRAS G12C inhibitor assigned to arm C.~ARM C: Patients receive combination therapy as in Arm A.
This phase II ComboMATCH treatment trial tests how well AMG 510 (sotorasib) with or without panitumumab in treating patients with KRAS G12C mutant solid tumors that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Sotorasib is in a class of medications called KRAS inhibitors. It works by blocking the action of the abnormal protein that signals cancer cells to multiply. This helps stop or slow the spread of cancer cells. Panitumumab is in a class of medications called monoclonal antibodies. It works by slowing or stopping the growth of cancer cells. Giving combination panitumumab and sotorasib may kill more tumor cells in patients with advanced solid tumors with KRAS G12C mutation.