KRAS-Directed Therapy Enters a New Era in Pancreatic Cancer: With Zev A. Wainberg, MD

Welcome to OncLive On Air®! I’m your host today, Courtney Flaherty.

OncLive On Air is a podcast from OncLive®, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, OncLive covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In this episode of OncLive On Air, Zev A. Wainberg, MD, sat down with OncLive to discuss the rapidly evolving landscape of KRAS-directed therapy in pancreatic ductal adenocarcinoma (PDAC), from pan-RAS inhibition to KRAS G12D–specific strategies, and what the next several years of clinical investigation may look like for patients with this difficult-to-treat malignancy.

Wainberg is a professor of medicine at the David Geffen School of Medicine at UCLA, co-director of the UCLA GI Oncology Program, and medical director of the UCLA Pancreas Cancer Center, where he also serves as director of the Early Phase Clinical Research Program at the Jonsson Comprehensive Cancer Center.

During the exclusive interview, Wainberg explored the scientific breakthroughs in structural chemistry that allowed researchers to finally target a protein long thought to be “undruggable,” as well as clinical data emerging on pan-RAS inhibition with daraxonrasib in the phase 3 RASolute-302 study (NCT07491445). He also detailed the design of the DAWN-303 trial (NCT07522073), a randomized phase 3 study evaluating investigator's choice chemotherapy with or without INCB161734 in patients with newly diagnosed, KRAS G12D–mutant advanced PDAC. INCB161734 is an investigational, potent on/off inhibitor of KRAS G12D, the most common KRAS alteration in PDAC.

Looking ahead, Wainberg expressed optimism that multiple KRAS inhibitors may ultimately be approved across different settings and lines of therapy and emphasized the importance of moving these agents into earlier disease stages.

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