Dr Pelster on the MAPKeeper 301 Trial Evaluating Atebimetinib in First-Line Metastatic Pancreatic Cancer

“This study does not require any particular biomarker… because of the mechanism [of action of atebimetinib] and the known overactivity of the MAP kinase pathway across pancreatic cancer. That’s a big advantage.”

Meredith Pelster, MD, MSCI, a medical oncologist and associate director of gastrointestinal cancer research at Sarah Cannon Research Institute, discussed the design of the phase 3 MAPKeeper 301 trial (NCT07562152) evaluating the MEK inhibitor atebimetinib (IMM-1-104) in combination with chemotherapy in patients with first-line metastatic pancreatic cancer, as well as the broader landscape of MAP kinase–directed therapy in the disease.

MAPKeeper 301 is enrolling patients who are newly diagnosed with metastatic pancreatic cancer, Pelster said. Patients will be randomly assigned to receive the novel combination of atebimetinib plus modified gemcitabine and nab-paclitaxel (Abraxane) or standard-of-care gemcitabine and nab-paclitaxel. The global, open-label study, which began enrolling in 2026, has a target enrollment of approximately 510 patients, with overall survival serving as the primary end point.

Importantly, the study does not require patients to have disease with any specific biomarker, therefore patients can enroll even if their molecular status is not yet known, Pelster emphasized. These broad enrollment criteria are due to atebimetinib’s mechanism of action and the known overactivity of the MAP kinase pathway across pancreatic cancer, she said.

Additionally, multiple ongoing frontline studies are investigating mutant-selective RAS inhibitors, Pelster noted. She explained how the field will be watching the outcomes of these phase 3 studies closely, as well as awaiting the MAPKeeper 301 data with atebimetinib. This collective research may surface the question of how best to select patients for certain therapies if multiple frontline treatment options ultimately become available, she added.

Treatment sequencing will also become an interesting question, according to Pelster. Clinical decision-making will depending on what treatment a patient is exposed to in the first-line setting, and it will become increasingly important to refer to data that show the efficacy of evolving second-line treatment approaches, she concluded.