Dr Wainberg on the Design of the DAWN-303 Trial of INCB161734 Plus Chemo in PDAC

“[KRAS inhibitors] are now going to be standard of care across the board.”

Zev A. Wainberg, MD, a professor of medicine at the University of California, Los Angeles (UCLA), and co-director of the UCLA GI Oncology Program, discussed the design of the ongoing phase 3 DAWN-303 trial (NCT07522073) evaluating the KRAS G12D inhibitor INCB161734 in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).

DAWN-303 is a randomized, double-blind study that recently launched and is already enrolling patients, Wainberg said. The trial uses investigator’s choice of chemotherapy: modified FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine plus nab-paclitaxel (Abraxane), he explained.

After the chemotherapy backbone is selected, patients are randomly assigned to receive that chemotherapy alone or in combination with INCB161734, Wainberg noted. The study is enrolling patients with previously untreated, KRAS G12D–mutated mPDAC, with a target enrollment of approximately 588 patients and primary end points of overall survival, progression-free survival, and objective response rate by blinded independent central review.

More broadly, Wainberg said that KRAS inhibitors are now poised to become standard of care across the board in pancreatic cancer. In August 2026, the FDA approved the KRAS inhibitor daraxonrasib (Rasonque) for the treatment adult patients with metastatic pancreatic adenocarcinoma who have received at least 1 prior systemic therapy or who are not eligible to receive multi-agent systemic therapy. With many other studies ongoing, it will take a number of years to clarify exactly which drug to use and during which step of disease management, according to Wainberg. He anticipates seeing a number of KRAS inhibitor approvals in pancreatic cancer over the coming years.

Clinical trials are also combining KRAS inhibitors with chemotherapy before surgery and in the adjuvant, among many other variables in how the drugs will ultimately be used and approved, Wainberg noted. Although sorting out exactly when and how will take several years, KRAS inhibitors will, in his opinion, become part and parcel of the treatment of every patient with pancreatic cancer.

This article was supported in part by Incyte. Content independently developed and published by OncLive.