Dr Ahn on Phase 2a Data With Atebimetinib and Chemotherapy in Pancreatic Cancer

“The questions that are going to potentially be pertinent in the future [will include:] how do we use all these novel targeted therapies? How does sequencing come into play, especially as all these studies are kind of going on at the same time, and especially since this is kind of an area of not only unmet need, but an area of uncharted territory.”

Daniel H. Ahn, DO, oncologist, internist, and professor of medicine at Mayo Clinic, discussed the results from a phase 2a trial (NCT05585320) presented at the 2026 ASCO Annual Meeting that evaluated the combination of atebimetinib and modified gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced or metastatic pancreatic cancer and previewed the forthcoming phase 3 MAPKeeper 301 trial (NCT07562152) in the same population.

In the phase 2a study evaluating the combination of gemcitabine and nab-paclitaxel with atebimetinib in treatment-naive patients with advanced pancreatic ductal adenocarcinoma (PDAC), investigators observed a median overall survival (OS) of 17.3 months (95% CI, 11.2-not reached), which compares favorably to a historical benchmark of approximately 10 months with gemcitabine/nab-paclitaxel alone, Ahn said.

The chemotherapy backbone was administered in a biweekly fashion on days 1 and 15 of each 28-day cycle, a schedule derived from prior work demonstrating that this modified dosing maintained treatment tolerability while reducing toxicity. The biweekly regimen, which is included in the NCCN guidelines for older patients, also facilitates integration with novel therapeutic agents, Ahn noted. Additionally, among 55 patients enrolled, the objective response rate (ORR) reached 36% (95% CI, 23%-51%) compared with the 20% to 30% range historically reported in the phase 3 pivotal trial of gemcitabine/nab-paclitaxel. Moreover, progression-free survival with standard chemotherapy has historically ranged from 5 to 6 months, whereas in the phase 2a trial it reached 8.3 months (95% CI, 5.9-9.6).

From a safety standpoint, the addition of atebimetinib did not introduce significant or unexpected toxicities beyond what would be anticipated from either agent individually, and the regimen was described as well tolerated, Ahn explained.

These findings are informing the design of MAPKeeper 301, a randomized phase 3 trial comparing gemcitabine plus nab-paclitaxel alone vs the combination with atebimetinib as first-line therapy in patients with advanced PDAC. The primary end point is OS. Ahn noted that ongoing questions remain around sequencing of novel targeted agents, including RAS inhibitors that have generated significant excitement in the refractory setting following the read out of the phase 3 RASolute 302 trial (NCT06625320).