In addition to eliciting 17.3 months median overall survival vs. 8.5 months for patients given standard of care treatment in a prior study, Immuneering’s atebimetinib demonstrated a robust tolerability profile—something CEO Ben Zeskind said equates highly with survival.
Immuneering’s investigational pancreatic cancer drug gave patients in a mid-stage trial nearly nine additional months of survival—adding another potential weapon to the quickly advancing next-gen treatment arsenal for the deadly disease.
In a Phase 2a trial, the MEK-targeting deep cyclic inhibitor atebimetinib plus modified gemcitabine/nab-paclitaxel (mGnP) elicited 17.3-months median overall survival (MOS), compared with 8.5 months for patients given gemcitabine/nab-paclitaxel in the pivotal Phase 3 MPACT study. Abraxane (nab-paclitaxel) in combination with gemcitabine, a regimen known as GnP, has been the standard of care for late-stage pancreatic cancer since Abraxane’s approval in 2013.
Median progression-free survival for the atebimetinib/chemotherapy combo was 8.3 months, while the disease control rate was 82%. The confirmed overall response rate was 36%.
The data come from 55 patients with first-line metastatic pancreatic cancer given 320 mg of atebimetinib plus mGnP. Immuneering first reported the overall survival results on May 21 and elaborated on the data Monday in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting.
These results for atebimetinib follow Revolution Medicines’ groundbreaking pancreatic cancer win, when its RAS inhibitor daraxonrasib doubled survival in the second line setting in a Phase 3 trial whose results were announced in April. In an interview with BioSpace prior to the ASCO presentation, Immuneering CEO Ben Zeskind put the company’s results into the context of the overall pancreatic cancer treatment space.
“We kind of have cancer surrounded,” he said. “Those RAS inhibitors are making a really good attack from the second line direction. We think 17.3 months is a really compelling median overall survival coming from the first-line direction.”
Zeskind also noted the consistency of atebimetinib’s results. In the original 34-patient cohort with a median follow-up of 17 months, MOS was likewise 17.3 months, according to Immuneering’s press release on Monday. “I think [it] really speaks to the robustness of the data,” he said.
Immuneering’s initial recruitment goal for the Phase 2a trial was 30 patients, but “there was just so much demand at our sites” because of what investigators were observing, and “we kind of took as many more patients as we could.”
Tolerability equals survival
Notably, the biotech observed only two categories of Grade 3 or higher treatment-related adverse events in at least 10% of participants—both of which Zeskind said were related to the chemo.
“I think the tolerability is certainly something to highlight,” Meredith Pelster, associate director of gastrointestinal cancer research at the Sarah Cannon Research Institute and an investigator on the Phase 2a trial, told BioSpace. “With the modified gemcitabine/nab-paclitaxel schedule, I’m not having to deal with the degree of cytopenias I typically would, and then the addition of atebimetinib, really we’re not seeing high-grade toxicity at all . . . . Keeping these patients on treatment is not challenging.”
While daraxonrasib appears to be extremely efficacious, it does come with some problematic side effects. The majority of patients on Revolution’s drug develop a rash—a side effect apparent in a recent 60 Minutes interview with former Nebraska Sen. Ben Sasse. Sasse credited daraxonrasib with decreasing his pain and reducing his tumor volume by 76%, USA Today reported, but a rash was evident on his face.
In the Phase 3 RASolute 302 trial, 43.6% of patients on daraxonrasib experienced a grade 3 or higher treatment-related adverse event (TRAE), compared to 57.5% of patients receiving chemo. However, just 1.2% of patients stopped treatment with Revolution’s drug due to these TRAEs.
Immuneering’s results “kind of redefine the tradeoffs” patients have to make, Zeskind said. “It used to be really that patients had to choose between survival and tolerability, between more time and the quality of that time, and I think the possibility that these data raise is that patients may have to make fewer trade-offs.”
Tolerability is not only important for quality of life, Zeskind added, but is also key to survival. When a patient’s status declines to a certain level on a key performance scale, he said, there is around a 48% increase in the risk of death. “Similarly, if they’re so beat up by the first-line therapy that they can’t go on to second-line therapy, in the literature, it’s about a 51% increase in the risk of death.”
In Immuneering’s trial, 84% of participants maintained or gained weight at three months—a particular challenge for patients with pancreatic cancer, according to Zeskind.
“The tolerability, the weight stability and gain, and the median overall survival—these are all, we think, important characteristics for a first-line treatment,” he said.
Next up, Immuneering intends to dose the first patient in the Phase 3 MAPKeeper 301 trial around the middle of this year. The biotech is planning to enroll around 510 patients in this study, Zeskind said, and expects to report topline results in mid-2028.
“We’re all very excited,” about the upcoming Phase 3 trial, said Pelster, who will also serve as an investigator on this study. “We need to prove that the combination is superior to standard of care, and when that happens, then we can really get this drug to people to make a difference.”
