Atebimetinib Plus SOC Chemo Improves Survival, Responses in Front-Line PDAC

Results from a phase 2a trial showed a 6-month OS and PFS rate of 94% and 72% compared with 67% and 44% from the phase 3 MPACT trial in the first-line treatment of PDAC.

Atebimetinib (IMM-1-104), an oral MEK inhibitor, in combination with modified gemcitabine and nab-paclitaxel (Abraxane) led to positive results, particularly regarding survival, in the frontline treatment of patients with pancreatic cancer in an ongoing phase 2a trial (NCT05585320), according to a press release from the developer, Immuneering Corporation.1

At the data cutoff of May 26, 2025, the overall survival (OS) and progression-free survival (PFS) 6-month rates were 94% (95% CI, 77%-98%) and 72% (95% CI, 50%-85%), respectively, at the 320 mg once-daily atebimetinib dose level (n = 32).2 As of the data cutoff, the median OS and PFS were not yet reached. The investigators noted that the standard of care benchmark for 6-month survival was 67% for OS and 44% for PFS in the phase 3 MPACT trial (NCT00844649).3

In response evaluable patients at both the 240 mg and 320 mg dose levels (n = 36), the overall response rate (ORR) was 39% (n = 14/36) and the disease control rate (DCR) was 81% (n = 29/36); deep, durable regressions were identified in many patients, and several individual lesions were rendered undetectable. Reference historical benchmarks showed an ORR of 23% (n = 99/431) and a DCR of 48% (n = 206/431).3

Additionally, 2 patients were refractory to the treatment combination with none during treatment, 4 patients were stabilized with eventual or potential escape with 1 while on treatment, and 23 patients were stabilized with durable or deepening RECIST sum of longest diameter for target lesions, including 17 while on treatment.

“The encouraging clinical data reported thus far for atebimetinib represent a potential new and significantly more durable treatment option for pancreatic cancer patients, for whom limited therapeutic options are currently available,” stated Vincent Chung, MD, FACP, professor in the department of Medical Oncology and Therapeutics Research at City of Hope, and principal investigator of the Phase 2a clinical trial, in the press release.1 “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, leading to poor patient outcomes.”

The trial enrolled a total of 34 patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in the treatment arm. Patients received atebimetinib at either 240 mg or 320 mg once-daily, and gemcitabine at 1000 mg/m2 plus nab-paclitaxel at 125 mg/m2 on days 1 and 15 every 4 weeks. The collected data was based on results from patients who received 320 mg of atebimetinib in the intention-to-treat population.

Eligible patients were 18 years or older with histologically or cytologically confirmed locally advanced unresectable or metastatic PDAC that has not received prior systemic anti-cancer therapy.4 Additionally, patients had an ECOG performance status of 0 or 1, at least one measurable target lesion per RECIST v1.1, and adequate organ function.

The median age of patients was 69 years, with 65% of patients 65 years or older. All patients had an ECOG performance status of 0 or 1, 65% were male, and 90% had elevated CA 19-9.

Regarding safety, grade 3 or higher adverse effects included anemia (18%), neutropenia (15%), hypokalemia (3%), vomiting (3%), and fatigue (3%). No patients experienced grade 5 toxicities.

The developer is currently planning a global randomized pivotal trial designed to facilitate accelerated approval that would compare atebimetinib plus gemcitabine and nab-paclitaxel vs gemcitabine and nab-paclitaxel alone in the first-line treatment of patients with PDAC.

“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,” concluded Chung. It was noted that Chung is a paid advisory board member of the drug’s developer.

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 17, 2025. https://tinyurl.com/2n8652y8
2. Outpacing cancer to help patients outlive their disease. Immuneering. June 2025. Accessed June 17, 2025. https://tinyurl.com/2srvzuuv
3. 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
4. A phase 1/​2a study of IMM-1-104 in participants with advanced or metastatic solid tumors. ClincialTrials.gov. Updated April 22, 2025. Accessed June 17, 2025. https://tinyurl.com/y8jf92w8