Varegacestat, a gamma secretase inhibitor, significantly improved progression-free survival while also meeting all key secondary endpoints in the pivotal RINGSIDE trial. Immunome is planning an FDA application for the second quarter of 2026.
Immunome is heading to the FDA with an application for varegacestat after the drug significantly improved progression-free survival in a Phase III trial of patients with progressing desmoid tumors.
In the pivotal RINGSIDE trial, varegacestat, an oral, once-daily gamma secretase inhibitor (GSI), elicited an 84% reduction in the risk of disease progression or death, meeting the study’s primary endpoint. Varegacestat also scored a 56% objective response rate, compared to 9% in placebo comparators, and led to statistically significant reductions in tumor volume and pain intensity, satisfying all key secondary trial endpoints, Immunome reported on Monday.
Immunome touted a “manageable” safety profile for its candidate, with diarrhea, fatigue and rash being the most commonly reported adverse events; most events were classified as grade 1 or 2.
With these results in hand, the Washington-based company plans to submit a new drug application for varegacestat to the FDA in this indication in the second quarter of 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,” Clay Siegall, the company’s CEO, said in a statement Monday.
Desmoid tumors are aggressive non-metastatic soft tissue malignancies that are prone to recurrence, according to Immunome. They cause debilitating pain, deformity and, in some instances, life-threatening organ damage. They afflict between 1,000 and 1,650 people in the U.S. each year.
In November 2023, the FDA approved SpringWorks Therapeutics’ Ogsiveo as the first drug for adults with desmoid tumors.
Ogsiveo’s nod was granted based on the Phase III DeFi trial, in which the drug, also a GSI, achieved a 71% reduction in the risk of disease progression. Median progression-free survival (PFS) was not reached in the Ogsiveo arm of the trial, while placebo comparators saw 15.1 months of PFS. Confirmed objective response was 41% for Ogsiveo vs. 8% for the placebo group in DeFi.
In Immunome’s statement Monday, Mrinal Gounder, sarcoma medical oncologist and drug development specialist at Memorial Sloan Kettering Cancer Center and primary investigator of the RINGSIDE trial, said the PFS benefit, high response rate and reduction in tumor volume seen with varegacestat in the trial were “striking.” He added, “These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors.”
