Immunome's Varegacestat Shows Promise in Phase III Desmoid Tumor Trial

Immunome, a Washington-based pharmaceutical company, has announced groundbreaking results from its Phase III RINGSIDE trial for varegacestat, a potential new treatment for desmoid tumors. The oral, once-daily gamma secretase inhibitor (GSI) demonstrated significant efficacy in improving progression-free survival and meeting all key secondary endpoints, positioning it as a strong contender for FDA approval.

Pivotal RINGSIDE Trial Results

The RINGSIDE trial, described as the largest and most comprehensive clinical study conducted to date in patients with desmoid tumors, revealed impressive outcomes for varegacestat:

• An 84% reduction in the risk of disease progression or death
• A 56% objective response rate, compared to 9% in the placebo group
• Statistically significant reductions in tumor volume and pain intensity

Dr. Clay Siegall, CEO of Immunome, highlighted the significance of these results, stating, "RINGSIDE... represents the highest objective response rate observed in a randomized clinical trial in this patient population."

Safety Profile and FDA Submission Plans

Immunome reported a "manageable" safety profile for varegacestat, with diarrhea, fatigue, and rash being the most commonly reported adverse events. The majority of these events were classified as grade 1 or 2.

Based on these promising results, Immunome plans to submit a new drug application (NDA) for varegacestat to the FDA in the second quarter of 2026.

Desmoid Tumors and Current Treatment Landscape

Desmoid tumors are aggressive, non-metastatic soft tissue malignancies that affect between 1,000 and 1,650 people in the U.S. annually. These tumors can cause debilitating pain, deformity, and in some cases, life-threatening organ damage.

The treatment landscape for desmoid tumors saw a significant development in November 2023 with the FDA approval of SpringWorks Therapeutics' Ogsiveo, the first drug specifically approved for adults with this condition. Ogsiveo, also a GSI, demonstrated a 71% reduction in the risk of disease progression in its Phase III DeFi trial.

Dr. Mrinal Gounder, sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center and primary investigator of the RINGSIDE trial, commented on varegacestat's potential impact: "These findings elevate the role of GSIs and confirm varegacestat could become standard of care in the treatment of desmoid tumors."