Atembimetinib Plus SOC Chemo Improves Survival/Safety in 1L PDAC

Atebimetinib (IMM-1-104) combined with modified gemcitabine and nab-paclitaxel (Abraxane) demonstrated positive survival and safety data as a frontline therapy for patients with pancreatic cancer, according to a press release from the developer, Immuneering.¹

The results came from an open-label, dose-exploration and expansion phase 1/2a trial (NCT05585320), which evaluated atebimetinib alone and with other approved agents in patients with RAS-mutated or RAS/MPK activated advanced or metastatic solid tumors.

With 9 months of median follow-up in 34 patients, the 9-month overall survival (OS) rate was 86% (CI, 66%-94%), though as of August 26, 2025, the median OS had not yet been reached. Notably, previously reported standard of care showed approximately 47% OS at 9 months. At 6 months, the OS rate was 94% (CI, 77%-98%) with the atebimetinib regimen vs approximately 67% with standard of care.

The 9-month progression-free survival (PFS) rate was 53% with the experimental regimen vs approximately 29% with standard of care; the 6-month PFS rate was 70% vs approximately 44%.

The estimates of standard of care were extrapolated and reconstructed by the developer based on results from the phase 3 MPACT trial (NCT00844649), which evaluated gemcitabine and nab-paclitaxel vs gemcitabine monotherapy in patients with pancreatic cancer.²

These data will be shared in full at the Pancreatic Cancer Action Network (PanCAN) Scientific Summit 2025.

The developer anticipates that regulatory feedback on plans for pivotal trials will be returned in Q4 of 2025; based on the feedback, they plan to initiate a pivotal phase 3 trial by the end of 2025, with the first patients to begin dosing by the middle of 2026.

“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,” said Vincent Chung, MD, FACP, professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, principal investigator of the Phase 2a clinical trial, and a paid member of the developer’s scientific advisory board, said.¹ “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 modified gemcitabine and nab-paclitaxel] in [patients with] first-line pancreatic cancer, now out to 9 months of median follow-up, represent an important step towards creating urgently needed new options for these patients. We are also planning a confirmatory study.”

A total of 34 patients were included in the efficacy analysis; all received 320 mg of atebimetinib once daily plus 1000 mg/m² of gemcitabine and 125 mg/m² of nab-paclitaxel.

Eligible patients were 18 years or older, and had measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and adequate organ function.³ For both phases of the trial with the combination therapy, patients had a locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma that had not received prior systemic anti-cancer therapy for their advanced or metastatic disease.

Patients were excluded from participation if they had symptomatic, untreated, or actively progressing known central nervous system metastases; impaired cardiovascular function or clinically significant cardiac disease; and receipt of an allogeneic tissue/solid organ transplant.

The primary end points of the phase 1 portion of the trial were adverse effects (AEs), dose-limiting toxicities, and the recommended phase 2 candidate optimal dose; in the phase 2a portion, it was the overall response rate. Secondary end points in the phase 2a portion included the disease control rate, PFS, OS, and duration of response.

Regarding safety, the most common AEs of grade 3 or higher were anemia (24%), neutropenia (18%), fatigue (6%), and vomiting, febrile neutropenia, hypokalemia, and nausea (3% each). No new safety signals were observed.

“Deep cyclic inhibitors like atebimetinib represent a fundamental shift in targeted therapy, away from continuous inhibition and toward pulsatile modulation of key oncogenic pathways,” said Brett Hall, PhD, chief scientific officer of Immuneering, in the release.¹ “This approach has the potential to deliver both durability and tolerability, 2 patient-centered essentials oncology has long struggled to balance.”

References

1. Immuneering announces extraordinary 86% overall survival at 9 months in first-line pancreatic cancer patients treated with atebimetinib + mGnP. News release. Immuneering Corporation. September 24, 2025. Accessed September 25, 2025. https://tinyurl.com/55jnm645
2. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1703. doi:10.1056/NEJMoa1304369
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 September 25, 2025. https://tinyurl.com/ymp2mx4h