Targeting KRAS Mutations in Advanced NSCLC - Episode 11

KRAS G12C Inhibition in Advanced NSCLC: MRTX849

David R. Gandara, MD: We want to talk about some of the other drugs in this class and then discuss acquired resistance. That speaks to your thoughts about the trials you’re involved with—we’re involved as well—and how you make this, and the other small-molecule inhibitors, better drugs.

Benjamin P. Levy, MD: Yes.

David R. Gandara, MD: The main competitor is from a company called Mirati Therapeutics, Inc, and I don’t actually know a name for this drug. It’s MRTX849. You know it because of the presentation. What’s the same? What’s different? Are all of these drugs going to be the same?

Benjamin P. Levy, MD: We don’t have as much data on MRTX849as we do with AMG 510. The last reported data on this looked at 17 patients with a similar design, a phase 1 study looking at patients with KRAS G12C with measurable disease. Most of these patients, if not all, had either non–small cell lung cancer or colorectal cancer. The last data we have are with 17 patients, of whom 12 had evaluable response. Of the 12 patients, there were 4 partial responses. Importantly, all the responses minus 1 were in lung cancer. There was 1 response in a patient with colorectal cancer. The drug is reasonably well tolerated, similar to AMG 510. There are some GI [gastrointestinal] toxicities, but we’re starting to see smaller numbers here compared with the AMG 510 drug. I don’t know at the end of the day if there will be clear differences or not between these 2 drugs, whether it will be similar to Coke versus Pepsi. I don’t know if you’ve heard or have had insights from your colleagues that there may be some preferential activity over AMG 510 or if there are differences in toxicity. I certainly haven’t heard that, and the data are somewhat early to comment on.

David R. Gandara, MD: My understanding is the same as yours. I will say, Ben, you’re quite familiar with the Lung-MAP, the Lung Cancer Master Protocol, which is a biomarker-driven master protocol and public-private partnership. Many of our audience will be participating in it. AMG 510 will be in a new study within Lung-MAP—and hopefully Mirati’s G12C inhibitor will be as well—looking at it in different populations and different combinations.

Transcript edited for clarity.