Encouraging Survival, Safety Data for Atebimetinib Combo in Pancreatic Cancer

The combination of atebimetinib (IMM-1-104) and modified gemcitabine/nab-paclitaxel (mGnP) in first-line pancreatic cancer exhibited impressive survival advantages during the phase 2a portion of a phase 1/2 trial (NCT05585320), surpassing standard-of-care benchmarks.¹

As of the data cutoff on August 26, 2025, data from the nonrandomized trial revealed that at a median follow up of 9 months, the overall survival (OS) and progression-free survival (PFS) among 34 patients receiving the combination therapy at the 320 mg once-daily dose were 86% and 53%, respectively. These findings compare favorably with the estimated 9-month OS and PFS standard-of-care benchmarks of 47% and 29%, extrapolated based on pivotal trial data from the MPACT (NCT00844649) study evaluating GnP in metastatic pancreatic cancer.

Compared with the OS of 94% and PFS of 72% revealed at the 6-month data readout in May 2025, these latest findings corroborate the promising durability of the combination and are particularly encouraging news for this tumor type, characterized by early metastasis, high mortality rates, and resistance to chemotherapy.²

Furthermore, the combination continued to demonstrate a favorable tolerability profile, as observed at 6 months. At 6 months, there were no observations of grade 3 or higher adverse events (AEs); at 9 months, neutropenia and anemia were the only categories of AEs observed at the grade 3 level with more than 10% incidence, with no new safety signals observed.

“Overall survival is the gold standard in oncology … 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% overall survival at 6 months sustained with additional follow up time, but that our observed 9-month overall survival of 86% shows an even larger gap with standard of care benchmarks,” said Ben Zeskind, PhD, chief executive officer of Immuneering, in a press release.¹ “To combine such meaningful overall survival with such favorable tolerability has the potential to be truly game-changing for first-line pancreatic cancer patients.”

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

What Is Atebimetinib’s Mechanism of Action?

Atebimetinib is an investigational oral dual MEK1/2 inhibitor³ that targets MEK in the MAPK pathway, which is pathologically activated in a majority of pancreatic cancers.¹ Additionally, as a deep cyclic inhibitor (DCI), atebimetinib is designed to induce slow, sustained tumor shrinkage and minimize impact on healthy cells, achieving both durability and tolerability.

“[DCIs] like atebimetinib represent a fundamental shift in targeted therapy, away from continuous inhibition and toward pulsatile modulation of key oncogenic pathways,” explained Brett Hall, PhD, chief scientific officer at Immuneering, in a press release.¹ “This approach has the potential to deliver both durability and tolerability, two patient-centered essentials oncology has long struggled to balance.”

What Are the Next Steps for the Trial?

Immuneering, the sponsor, expects regulatory feedback on their planned pivotal phase 3 trial in the coming months, which they hope to subsequently initiate by the end of 2025 and begin dosing patients by mid-2026.¹ Other activities planned for 2026 include a further updated report of survival data at a scientific conference and addition of combination arms investigating the combination in other tumor types, such as non–small cell lung cancer.

REFERENCES:

1. 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 October 6, 2025. https://tinyurl.com/yj8nuhxd

2. Zeng S, Pöttler M, Lan B, et al. Chemoresistance in Pancreatic Cancer. International Journal of Molecular Sciences. 2019;20(18):4504-4504. doi:https://doi.org/10.3390/ijms20184504

3. A Phase 1/2a, Open-Label, Multicenter, Nonrandomized, Safety and Anti-tumor Activity Study of IMM-1-104, a Novel Oral Dual MEK1/2 Inhibitor in Participants With Advanced or Metastatic Solid Tumors. ClinicalTrials.gov. Updated September 2, 2023. Accessed October 6, 2025. https://clinicaltrials.gov/study/NCT05585320