Clinical Trials Spotlight - KRAS G12c

Oncology CTSU Supporting First-in-Human Study Evaluating KRAS G12c Protein Inhibitor

The Oncology CTSU is supporting a first-in-human study evaluating the efficacy of an irreversible oral inhibitor of the oncogene KRAS G12c, led by Principal Investigator John C. Krauss, MD, and supported by O-CTSU Study Coordinators Dominique Dippman and Kate Moran. 

The KRAS G12c mutation is found in lung cancer, colon cancer, and various other cancers. KRAS G12c is particularly challenging because there is a lack of traditional small molecule binding sites on the KRAS protein. AMGEN, the study sponsor, is supplying the study drug AMG-510, and the trial is being conducted at Michigan Medicine and selected medical centers throughout the world. AMG 510 binds to sites on the KRAS protein, inhibiting the proliferation of cancer cells. Preliminary results of the trial presented at the American Society of Clinical Oncology in June 2019 and the European Society for Medical Oncology in September 2019, demonstrated very promising tumor control rates and very little toxicity.

This first-in-human study includes two cohorts, AMG 510 monotherapy and AMG 510 in combination with pembrolizumab, an antibody used in immunotherapy. The monotherapy cohort will evaluate the safety and tolerability of AMG 510 in subjects with KRAS mutant advanced solid tumors and estimate the maximum tolerated dose and/or recommended Phase 2 dose. The combination cohort will be to evaluate the safety and tolerability of AMG 510 in combination with pembrolizumab in subjects with the KRAS G12c mutant advanced non-small cell lung cancer. 

“We are excited to be one of the medical centers participating in this early phase of clinical research with such a promising cancer treatment.” said Patty Bebee, an Oncology-CTSU Portfolio Manager. “We currently have two new AMG 510 studies in the study start-up phase we hope will also show promise.” 

A planned Phase 2 portion of the study will have a primary objective to evaluate tumor objective response rate (ORR) assessed by RECIST 1.1 criteria of AMG 510 as monotherapy in subjects with KRAS p.G12C mutated advanced tumors.