Atebimetinib Combo Shows Compelling 1-Year OS in First-Line Pancreatic Cancer

In the latest update from a phase 2a trial (NCT05585320) investigating the combination of atebimetinib (IMM-1-104) plus modified gemcitabine/nab-paclitaxel (mGnP) in patients with pancreatic cancer, 1-year survival data showed encouraging, sustained overall survival (OS) benefits that meaningfully exceeds historical expectations in the frontline setting.¹

As of the latest data cut-off on December 15, 2025, the 12-month overall survival (OS) rate was 64% among patients receiving the combination therapy at the 320-mg once-daily dose (n = 34), demonstrating durability of the survival signal as reported in September 2025, which reported an 86% OS at 9 months.²

The survival data represent a significant benchmark in a disease state where long-term outcomes remain historically poor. Pancreatic cancer continues to be one of the most difficult-to-treat malignancies, characterized by a high prevalence of RAS mutations that drive aggressive tumor growth and resistance to standard cytotoxic therapies.

Along with the positive efficacy data, the combination exhibited a manageable safety profile, with no new safety signals observed.¹ Grade 3 events of neutropenia and anemia were observed in more than 10% of patients but were expected with standard-of-care chemotherapy and remained consistent with the previous data report.

“The [OS] data reported for atebimetinib demonstrate its potential to be a better treatment option for patients with pancreatic cancer, for whom there is a need for more durable and better-tolerated treatments,” said Meredith Pelster, MD, investigator and associate director of gastrointestinal cancer research at Sarah Cannon Research Institute, in a news release.¹ “Looking ahead, I share the enthusiasm of many in the field for the planned atebimetinib pivotal [p]hase 3 clinical trial and look forward to enrolling patients in the program."

Atebimetinib is an investigational oral deep cyclic inhibitor that targets MEK in the MAPK pathway, which is activated in many solid tumors including pancreatic cancer. Its mechanism of action is designed to induce slow but durable tumor shrinkage that outpaces the tumor’s ability to develop resistance.

In 2024, the FDA granted atebimetinib fast track designation for treatment of patients with pancreatic adenocarcinoma (PDAC) who have progressed after 1 line of treatment.

About the Phase 2a Trial

The phase 2a portion of the phase 1/2 trial is an open-label, multicenter study designed to evaluate the safety, tolerability, and antitumor activity of atebimetinib in combination with mGnP in patients with RAS-mutant or RAS/MAPK activated advanced or metastatic solid tumors, with a specific expansion cohort dedicated to first-line PDAC.² Other cancer types investigated include non–small cell lung cancer and malignant cutaneous melanoma.

Participants in the frontline PDAC cohort received atebimetinib at the recommended phase 2 dose in combination with mGnP. The primary objectives of the trial included evaluating the objective response rate and safety, with secondary objectives focusing on progression-free survival, duration of response, and OS.

Earlier data from the trial had already indicated signs of tumor regression and durable disease control. The maturation of the OS data provides the strongest evidence to date that the addition of a cyclic MEK inhibitor may fundamentally alter the natural history of the disease for a subset of patients.

Next Steps in Development

Based on these positive results, trial sponsor Immuneering plans to advance the development of atebimetinib rapidly. Following interactions with the FDA and European Medicines Agency (EMA), the parties have aligned on the design of the planned pivotal phase 3 trial, MAPKeeper 301, in which the first patient is expected to be dosed in mid-2026. OS has been selected as the primary end point of the trial.

If the survival trend holds in larger cohorts, atebimetinib could represent a significant advance for MEK-targeted therapies to successfully integrate into the frontline treatment landscape for pancreatic cancer.

REFERENCES

1. Immuneering announces exceptional 64% overall survival at 12 months in first-line pancreatic cancer patients treated with atebimetinib + mGnP. News release. Immuneering. January 7, 2026. Accessed January 27, 2026. https://tinyurl.com/yc4jvxrf

2. 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 January 27, 2026. https://tinyurl.com/yj8nuhxd

3. A phase 1/2a study of IMM-1-104 in participants with advanced or metastatic solid tumors. ClinicalTrials.gov. Updated September 2, 2025. Accessed January 27, 2026. https://clinicaltrials.gov/study/NCT05585320