The combination of atebimetinib (IMM-1-104) and modified gemcitabine/nab-paclitaxel (Abraxane; mGnP) elicited relatively high survival rates compared with historical standard-of-care (SOC) data at a median follow-up of 9 months in patients with treatment-naive pancreatic cancer, according to updated findings from the phase 2a portion of an ongoing phase 1/2 trial (NCT05585320).1
At a data cutoff date of August 26, 2025, among 34 evaluable patients, the 9-month overall survival (OS) rate with the combination was 86% (95% CI, 66%-94%), and the median OS was not reached; in an illustrative comparison with historical SOC data, this rate with the SOC benchmark regimen of gemcitabine plus nab-paclitaxel was approximately 47% in the pivotal phase 3 MPACT trial (NCT00844649). Additionally, the 9-month progression-free survival (PFS) rate with atebimetinib plus mGnP was 53%; this rate was approximately 29% with SOC in MPACT.
“Pancreatic cancer remains one of the most challenging cancers we face in the clinic with far too few treatment options available to patients and survival rates that have remained unacceptably low for decades,” Vincent Chung, MD, FACP, a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Duarte, California, as well as the principal investigator of the phase 2a trial and a paid member of Immuneering’s scientific advisory board, stated in a news release. “I have seen firsthand in my own patients the benefits of atebimetinib’s durability and tolerability. The remarkable OS, PFS, and tolerability data we are seeing with atebimetinib plus mGnP in [patients with] first-line pancreatic cancer, now out to 9 months of median follow-up, represent an important step toward creating urgently needed new options for these patients. We are also planning a confirmatory study.”
Atebimetinib Plus mGnP in Pancreatic Cancer: Phase 2a Trial Key Takeaways
- The combination of atebimetinib and mGnP generated a 9-month OS rate of 86% in patients with treatment-naive pancreatic cancer, exceeding the approximate 47% 9-month OS rate observed with the historical SOC benchmark regimen in the MPACT trial.1
- Atebimetinib functions as a MEK-targeting deep cyclic inhibitor, a class of agents designed for pulsatile modulation to shrink tumors gradually and more durably than sustained inhibition.
- The combination of atebimetinib plus mGnP continued to exhibit a favorable safety profile with extended follow-up. No new safety signals or grade 5 AEs were reported.
Immuneering, the developer of atebimetinib, expects to receive regulatory feedback in the fourth quarter of 2025 regarding its plans for a pivotal trial. Based on that feedback, the company plans to initiate the pivotal trial by the end of 2025 and begin dosing patients by the middle of 2026. Further updated OS and PFS data from the phase 2a trial are also planned to be presented at a scientific meeting in 2026.
“OS is the gold standard in oncology and has been Immuneering’s goal from the beginning,” Ben Zeskind, PhD, cofounder, president, and chief executive officer of Immuneering, added in the news release. “In cancer, nothing matters more than keeping patients alive and helping them thrive. We are beyond thrilled to report that not only was our extraordinary 94% OS [rate] at 6 months sustained with additional follow-up time, but our observed 9-month OS [rate] of 86% shows an even larger gap [compared with] SOC benchmarks. To combine such meaningful OS with such favorable tolerability has the potential to be truly game-changing for [patients with] first-line pancreatic cancer.”
What Is the Mechanism of Action of Atebimetinib?
Atebimetinib is a MEK-targeting deep cyclic inhibitor, part of a class of agents that is designed to pulse quicker than tumor reaction times, shrinking tumors gradually and more durably than agents that employ sustained inhibition and may trigger tumors to adapt and develop treatment resistance. Sustained inhibition is also associated with suppressed transient signaling in healthy cells, which can lead to adverse effects (AEs). In comparison, deep cyclic inhibitors restore full transient signaling abilities to healthy cells and may therefore lead to fewer AEs.
