Spira on ctDNA in KRAS G12D Pancreatic Cancer and Zoldonrasib

Alexander I. Spira, MD, PhD, FACP, co-director of Virginia Cancer Specialists Research Institute, director of the Thoracic and Phase I Program, and clinical assistant professor at Johns Hopkins School of Medicine, discusses the clinical implications of circulating tumor DNA (ctDNA) findings presented at the 2025 Gastrointestinal Cancers Symposium for treatment decisions and monitoring in patients with KRAS G12D pancreatic ductal adenocarcinoma treated with zoldonrasib (RMC-9805).

He then discusses how this information might guide treatment strategies in the real-world setting.

Transcription:

0:10 | ctDNA is one of those things that we are really learning a lot more about. Of course, we work with it for regulatory reasons. Response rate is the number one thing we look at, and the number two thing we look at, of course, all the time. However, we also know that in some of these patients, especially in the heavily pretreated population, response rate does not always correlate with clinical benefit rate. That is why we look at overall survival and progression-free survival [PFS] as well.

0:33 | What we found here was some fairly impressive numbers. If you look at what we call variant allele frequency, or VAF, 39% of patients had a 100% decrease in their KRAS G12C or G12D VAF, and 86% of patients had at least a 50% decline in that number. That tells us a couple of things: it tells us that patients who are responding—patients who are responding but not showing it on imaging—are also doing very well.

1:04 | And that goes into the clinical benefit rate, and we hope into the overall survival rate. We know it’s a nice way of getting an idea of what’s going on before you get those overall survival signals, as well as early on, even before you get a scan. Can you see some kind of benefit there? So, this tells us we are getting benefit from the drug in multiple different ways, which can lead us to larger studies, phase 3 studies, and likely improvements in overall survival and PFS. We hope, of course, as we get to those study designs.