The data cutoff for the current analysis is April 24, 2026. Baseline characteristics in the expanded cohort are as follows:
- Median age: 68 years (range, 42-85); 62% of patients were aged 65 or older
- Disease status: 96% metastatic, 4% locally advanced
- ECOG PS: 0 in 56%, 1 in 44%
- CA 19-9 elevated (≥37 U/mL): 89% of evaluable participants
- Presence of liver metastasis: 51%
- Presence of peritoneal metastasis: 36%
- Presence of lung metastasis: 27%
- De novo metastatic disease: 51%
- Mutation status: KRAS-mutant disease: 87%; RAS mutations unknown: 13%
Of note, 60% of patients who came off study treatment received second-line treatment.
What additional efficacy outcomes from the expanded cohort were reported?
At the data cutoff, 11 patients in the expanded cohort were still on treatment and 44 had come off treatment. Of those 44, twenty-one went on to receive subsequent cancer therapy, 14 did not, and 9 were unknown. Of the patients who received subsequent therapy, 20 went on to receive chemotherapy and/or radiation and 1 to receive a RAS inhibitor.
Furthermore, approximately half of patients were still alive at the data cutoff. Vu noted that the OS Kaplan-Meier curve showed gradual early decline followed by separation from historical comparators that was maintained throughout the observation period, suggesting a subset of participants deriving durable benefit rather than a uniform shift in the survival distribution. He cautioned that no head-to-head trial has been conducted comparing atebimetinib with other candidates, and cross-trial comparisons are hypothesis-generating only.
What was the safety profile of atebimetinib plus mGnP?
The tolerability profile of atebimetinib plus mGnP was notable for the absence of significant MEK inhibitor class toxicities at higher grades. Grade 3 or higher anemia and neutropenia each occurred in over 10% of patients, but both were attributed to the chemotherapy backbone. Treatment-related adverse effects (TRAEs) occurring in 20% or more of patients (any grade; grade 3 or higher) included fatigue (53%; 2%), nausea (45%; 0%), anemia (42%; 16%), rash (36%; 5%), diarrhea (36%; 0%), vomiting (29%; 2%), alopecia (27%; 0%), dysgeusia (27%; 0%), peripheral edema (27%; 2%), neutropenia (25%; 18%), peripheral neuropathy (22%; 0%).
The only MEK inhibitor class effect reaching grade 3 or higher was rash, occurring in 5% of participants and resolving with medical management. Ocular, cardiac, and diarrhea events, when observed, were grade 1/2 and did not result in any discontinuations. Only 1 patient in the expanded cohort discontinued atebimetinib over the course of the study, and that discontinuation was not due to toxicity; the participant continued chemotherapy. Notably, 84% of participants were weight stable or gained weight at 3 months — a finding the investigators highlighted as meaningful in a disease defined by cachexia.
Vincent Chung, MD, a medical oncologist at City of Hope Cancer Center in Duarte, California, and a co-investigator on the study, reflected on this tolerability signal in a Q&A session following the presentation. "[Atebimetinib] has a short half-life, so it's out of the system very quickly. This is why we're not seeing the same toxicities that we've seen with first- and second-generation MEK inhibitors," he explained.
When asked about patient QOL with atebimetinib in the ensuing Q&A, Vu noted that, "In my experience, treating a lot of patients on this study, patients have done incredibly well from a QOL perspective. It's been remarkable to see how they have felt very well throughout the study period. I was talking to Dr. Chung and he also has patients with a similar experience, where they're on study for a few years and still feeling very minimal AEs."
What study limitations and unanswered questions were acknowledged? How will MAPKeeper 301 seek to address them?
As a single-arm trial without a control group, efficacy and tolerability of the combination cannot be directly compared with standard of care (SOC), Vu emphasized. He noted that follow-up in the expanded cohort is still maturing and the OS upper confidence bound has not yet been reached. Moreover, the second-line treatment rate of 60%, while encouraging, cannot be definitively attributed to atebimetinib's tolerability without a randomized comparator. Additionally, the modified GnP schedule used in the study, which is administered on days 1 and 15 rather than the standard weekly regimen, differs from the full standard-dose approach, leaving the independent contribution of that dose modification to this outcome unknown.
These are all the questions that the MAPKeeper 301 trial is designed to answer. MAPKeeper 301 is a randomized, global study comparing atebimetinib plus mGnP against SOC gemcitabine and nab-paclitaxel at the full weekly schedule in patients with first-line metastatic PDAC.1,2 The trial is currently recruiting with a target population of 225 participants per arm. The primary end point is OS, with secondary end points of PFS, DCR, ORR, and QOL. Stratification factors include geography (United States vs rest of world), liver metastasis (present vs absent), ECOG PS (0 vs 1), and disease presentation (de novo vs recurrent /metastatic).
Disclosures: Vu disclosed no relevant relationships with companies.
References
- Chung V, Vu P, Ma VT, et al. Results from a phase 2a study of atebimetinib in combination with mGnP in first-line metastatic pancreatic cancer. J Clin Oncol. 2026;44(16 suppl):4013. doi:10.1200/JCO.2026.44.16_suppl.4013
- Atebimetinib + GnP as a first line treatment in patients With metastatic pancreatic adenocarcinoma (MAPKeeper 301). ClinicalTrials.gov. Updated May 15, 2026. Accessed June 1, 2026. https://clinicaltrials.gov/study/NCT07562152
