Amgen: 5 patients experienced partial response in AMG 510 Phase 1 study
Amgen announced the first clinical results from a Phase 1 study evaluating investigational AMG 510, the first KRASG12C inhibitor to reach the clinical stage. In the trial, there were no dose-limiting toxicities at tested dose levels. AMG 510 showed anti-tumor activity when administered as a monotherapy in patients with locally-advanced or metastatic KRASG12C mutant solid tumors. These data are being presented during an oral session at the 55th Annual Meeting of the American Society of Clinical Oncology in Chicago. The Phase 1, first-in-human, open-label multicenter study enrolled 35 patients with various tumor types. Eligible patients were heavily pretreated with at least two or more prior lines of treatment, consistent with their tumor type and stage of disease. The primary endpoint is safety, and key secondary endpoints include pharmacokinetics, objective response rate, duration of response and progression-free survival. Patients were enrolled in four dose cohorts - 180 mg, 360 mg, 720 mg and 960 mg, taken orally once a day. Five out of 10 evaluable patients with NSCLC experienced a partial response, and another four had stable disease, for a disease control rate of 90 percent. All five patients with response to therapy had a treatment duration of 7.3-27.4 weeks at data cutoff and remain active on treatment. One patient with PR improved further to a complete response of the target lesions at week 18, post data cutoff. In addition, 13 of 18 evaluable patients with CRC achieved SD, with the majority of CRC patients treated at the first two dose levels. Twenty-six patients remain on study and nine have discontinued. "KRAS has been a target of active exploration in cancer research since it was identified as one of the first oncogenes more than 30 years ago, but it remained undruggable due to a lack of traditional small molecule binding pockets on the protein. AMG 510 seeks to crack the KRAS code by exploiting a previously hidden groove on the protein surface," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "By irreversibly binding to cysteine 12 on the mutated KRAS protein, AMG 510 is designed to lock it into an inactive state. With high selectivity for KRASG12C, we believe investigational AMG 510 has high potential as both a monotherapy and in combination with other targeted and immune therapies."