Immunome Announces Positive Topline Results from Phase 3 RINGSIDE Trial of Varegacestat in Patients with Desmoid Tumors

Immunome, Inc. (Nasdaq: IMNM), a biotechnology company committed to developing first-in-class and best-in-class targeted cancer therapies, today announced positive topline results from the global pivotal Phase 3 RINGSIDE trial of varegacestat, an investigational, oral, once-daily gamma secretase inhibitor (GSI), in patients with progressing desmoid tumors.

The trial met its primary endpoint of improving progression-free survival, demonstrating a statistically significant and clinically meaningful improvement vs. placebo, with an 84% reduction in the risk of disease progression or death (hazard ratio (HR) = 0.16, 95% CI: 0.071, 0.375; p<0.0001). The confirmed objective response rate (ORR) based on RECIST v1.1 was 56% with varegacestat vs. 9% with placebo (p<0.0001), as assessed by blinded independent central review. In an exploratory analysis, varegacestat demonstrated a median best change in tumor volume of -83% vs. +11% with placebo, as assessed by blinded independent central review. In addition, the trial met all key secondary endpoints, with varegacestat achieving statistically significant improvements vs. placebo in landmark tumor volume reduction and worst pain intensity.

Varegacestat was generally well tolerated, with a manageable safety profile consistent with the GSI class. The most common adverse events for participants in the treatment arm were diarrhea (82%), fatigue (44%), rash (43%), nausea (35%) and cough (34%). Most events were grade 1 or 2.

Based on these data, Immunome plans to submit a New Drug Application to the U.S. Food and Drug Administration in Q2 2026.

“RINGSIDE is the largest and most comprehensive clinical trial conducted to date in patients with desmoid tumors, and the topline results represent the highest objective response rate observed in a randomized clinical trial in this patient population,” said Immunome’s CEO Clay Siegall, Ph.D. “These findings demonstrate the potential of varegacestat to offer best-in-class results in a convenient, once-daily, oral medicine that may help patients reclaim their lives.”

“Desmoid tumors can have a devastating physical and emotional impact on patients given their unpredictable nature and the limitations of current treatment options,” said Mrinal M. Gounder, M.D., sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center, and RINGSIDE primary investigator. “The progression-free survival benefit, high response rate and reduction in tumor volume with varegacestat in the RINGSIDE trial are striking. These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors.”