Atebimetinib Combo Shows Survival Signal in First-Line Pancreatic Cancer

Atebimetinib combined with gemcitabine/nab-paclitaxel showed signs of improved survival in the first-line setting.

First-line treatment with the oral, novel MEK inhibitor atebimetinib (IMM-1-104) in combination with modified gemcitabine (Gemzar) and nab-paclitaxel (Abraxane) generated signs of survival benefit in patients with pancreatic cancer, according to data from the phase 2a portion of a phase 1/2 trial (NCT05585320).¹

Findings announced by Immuneering showed that evaluable patients treated with atebimetinib at 320 mg once per day plus modified gemcitabine and nab-paclitaxel (n = 34) achieved a 6-month overall survival (OS) rate of 94%, and the median OS was not reached (NR). Additionally, the median progression-free survival (PFS) was also NR, and the 6-month PFS rate was 72%.

“The encouraging clinical data reported thus far for atebimetinib represent a potential new and significantly more durable treatment option for [patients with] pancreatic cancer, for whom limited therapeutic options are currently available,” Vincent Chung, MD, FACP, a professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, and principal investigator of the phase 2a clinical trial, stated in a news release. “I have treated [patients with] pancreatic cancer with atebimetinib who have experienced exceptional durability. Current standard-of-care therapies in pancreatic cancer can be associated with limited durability and severe [adverse] effects [AEs], leading to poor patient outcomes. We have not seen significant improvement in standard of care for decades, and there is an urgent need for more durable and better tolerated new treatments that help patients live longer.”

Atebimetinib Trial Background

The phase 1/2, open-label, dose-exploration and -expansion study is evaluating atebimetinib both as monotherapy and in combination with approved agents in patients with advanced or metastatic solid tumors harboring RAS mutations or RAS/MAPK activation.²

Patients need to be at least 18 years of age to enroll. For the monotherapy portions of the study, participants are required to have any locally advanced or metastatic solid tumors harboring a RAS activating mutation for phase 1. Phase 2a is restricted to patients with pancreatic ductal adenocarcinoma (PDAC), RAS-mutant melanoma, or RAS-mutant non–small cell lung cancer.

Patients with locally advanced or metastatic PDAC are eligible to enroll in a combination cohort in both phases of the study. Phase 2a also includes combination arms for patients with stage III/IV cutaneous melanoma whose disease progressed after receiving anti–PD-(L)1 therapy as their most recent line of therapy. One arm will include patients with BRAF mutations, and the other does not require BRAF mutations.

For the PDAC combination cohorts, no prior systemic anticancer therapy in the advanced or metastatic setting is allowed, and patients also need to have evidence of measurable disease with at least 1 target lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.

In treatment group B, patients with first-line PDAC are receiving atebimetinib in combination with gemcitabine at 1000 mg/m² and nab-paclitaxel at 125 mg/m². Another cohort is assessing atebimetinib plus FOLFIRINOX (fluorouracil, oxaliplatin, and irinotecan) in the first-line treatment of patients with advanced PDAC.

Overall response rate (ORR) is the primary end point of the phase 2a portion of the study. Secondary end points include pharmacokinetics, PFS, OS, and duration of response.

Additional Phase 2a Data

Among patients who received atebimetinib at a dose of 240 mg or 320 mg in combination with modified gemcitabine and nab-paclitaxel (n = 36), the ORR was 39%, and the disease control rate was 81%.

Regarding safety, no grade 3 or higher AEs were reported in the major AE categories associated with first-line chemotherapy in PDAC. This cohort will continue enrolling to a target population of approximately 50 patients.

“These exceptional data demonstrate the potential of atebimetinib plus modified gemcitabine and nab-paclitaxel to dramatically extend the lives of patients with advanced pancreatic cancer,” Ben Zeskind, PhD, co-founder and chief executive officer of Immuneering, added in a news release. “[A] 94% OS [rate] at 6 months is remarkable in [patients with] first-line pancreatic cancer. Atebimetinib was designed to deliver exceptional durability and tolerability to a broad range of patients with different cancers, and it is deeply gratifying to see evidence of that playing out first in one of the most aggressive and deadly types of cancer. Our ultimate goal is to help [patients with] cancer outlive their disease, and today’s announcement represents an important milestone on that journey.”

References

1. 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 June 18, 2025. https://ir.immuneering.com/news-releases/news-release-details/immuneering-reports-positive-overall-survival-data-atebimetinib
2. A phase 1/​2a study of IMM-1-104 in participants with advanced or metastatic solid tumors. ClinicalTrials.gov. Updated April 22, 2025. Accessed June 18, 2025. https://clinicaltrials.gov/study/NCT05585320