Fakih's phase 1 trial targets the KRAS G12C mutation with AMG510, a drug that suppresses tumor growth when taken orally. KRAS G12C is a cancer-associated gene mutation that occurs in around 13% of nonsmall cell lung cancer cases, as well as 3%-5% of colorectal cancers and up to 2% of other solid tumor cancers, including pancreatic. Initial results of the trial were presented by Fakih on June 3 at the 55th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
Twenty-nine patients were enrolled in the trial, including 10 patients with lung cancer, 18 patients with colorectal cancer and one patient with appendix cancer. Nine of the 10 lung cancer patients showed a clinical benefit, with five patients having partial responses and four patients having stable (nonprogressive) disease. Five had tumors shrink in size by at least 50%. Among the 19 patients with colorectal and appendiceal cancer, 14 patients experienced stable disease.
No serious side effects were reported, and treatment-related adverse events were uncommon.
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“These findings are exciting and potentially practice-changing,” Fakih said. “It is not often that we experience robust efficacy with a targeted therapy without seeing substantial toxicity. The major responses noted in lung cancer are a proof of principle of the rational design and activity of this agent.”
Fakih said the study continues at the recommended dose of 960 mg daily in expansion cohorts of lung, colon, and other solid tumors.
“Additional results from this ongoing study will help guide us further in the development of AMG510 in key solid tumors with KRAS G12C mutation,” he said.
An update to the study’s original abstract was published June 3 in ASCO’s Journal of Clinical Oncology, which you can read here.