Immunome, a biotechnology company focused on first-in-class and best-in-class targeted cancer therapies, has announced striking topline results from its global Phase 3 RINGSIDE trial of varegacestat, an oral, once-daily gamma secretase inhibitor (GSI), in patients with progressing desmoid tumors.

 

The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival, with an 84% reduction in the risk of disease progression or death. The confirmed objective response rate (ORR) was 56% for varegacestat vs. 9% for placebo. Exploratory analyses showed a median tumor volume reduction of 83% with varegacestat vs. an 11% increase on placebo.

 

Varegacestat also met all key secondary endpoints, including landmark tumor volume reduction and worst pain intensity, and was generally well tolerated. Most adverse events—diarrhea (82%), fatigue (44%), rash (43%), nausea (35%), and cough (34%)—were grade 1 or 2 and consistent with the GSI class.

 

Based on these results, Immunome plans to submit a New Drug Application to the FDA 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 CEO Clay Siegall. 

 

“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, Sarcoma Medical oncologist 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.”

 

Siegall added, “The RINGSIDE results represent a major milestone for Immunome as we advance our emerging pipeline of targeted oncology therapies that have exceptional potential to meaningfully improve the lives of patients.”