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.”
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.
“Deep cyclic inhibitors like atebimetinib represent a fundamental shift in targeted therapy, away from continuous inhibition and toward pulsatile modulation of key oncogenic pathways,” Brett Hall, PhD, chief scientific officer at Immuneering, added in the news release. “This approach has the potential to deliver both durability and tolerability, two patient-centered essentials oncology has long struggled to balance.”
What Is the Design of the Phase 1/2 Trial Investigating Frontline Atebimetinib in Pancreatic Cancer?
The first-line pancreatic cancer combination portion of the trial enrolled patients at least 18 years of age with histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma who had received no prior systemic anticancer therapy.2 Patients also needed to have measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.
Patients in this arm received atebimetinib at 320 mg once daily plus mGnP.1
Overall response rate serves as the primary end point of the phase 2a portion.2 Secondary end points in this portion include pharmacokinetics, disease control rate, PFS, duration of response, 3-month survival outcomes, 6-month survival outcomes, and OS.
What Findings Have Been Previously Reported From the Phase 2 Portion of the Trial of First-Line Atebimetinib Plus mGnP in Pancreatic Cancer?
Notably, at a median follow-up of 6 months, the OS rate was 94% (95% CI, 77%-98%) with atebimetinib plus mGnP; this rate was 67% among patients who received SOC in MPACT.1,3 The 6-month PFS rates were 70% and approximately 44% in these respective arms.1
What Is the Safety Profile of First-Line Atebimetinib Plus mGnP in Pancreatic Cancer?
With extended follow-up, the combination continued to show a favorable safety profile, and no new safety signals were reported, according to the news release. The most frequently observed grade 3 or higher AEs were anemia (24%), neutropenia (18%), fatigue (6%), vomiting (3%), febrile neutropenia (3%), hypokalemia (3%), and nausea (3%). No grade 5 AEs were observed.
References
- Immuneering announces extraordinary 86% overall survival at 9 months in first-line pancreatic cancer patients treated with atebimetinib + mGnP. News release. Immuneering. September 24, 2025. Accessed September 25, 2025. https://ir.immuneering.com/news-releases/news-release-details/immuneering-announces-extraordinary-86-overall-survival-9-months
- A phase 1/2a study of IMM-1-104 in participants with advanced or metastatic solid tumors. ClinicalTrials.gov. Updated September 2, 2025. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT05585320?a=8
- Immuneering reports positive overall survival data for atebimetinib (IMM-1-104) from ongoing phase 2a trial in first-line pancreatic cancer patients. News release. Immuneering. June 17, 2025. Accessed September 25, 2025. https://ir.immuneering.com/news-releases/news-release-details/immuneering-reports-positive-overall-survival-data-atebimetinib
