Immunome’s gamma secretase inhibitor varegacestat cut the risk of desmoid tumor progression or death by 84% in the Phase 3 RINGSIDE trial, delivering durable efficacy, rapid pain relief, and manageable safety. ASCO 2026 results support its potential as a new standard of care, with FDA and EMA filings underway.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Immunome has presented detailed Phase 3 results from the pivotal RINGSIDE trial of varegacestat at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The investigational gamma secretase inhibitor reduced the risk of disease progression or death by 84% compared with placebo (HR=0.16; p<0.0001), confirming a significant clinical benefit in patients with progressing desmoid tumors.
Durable Efficacy Across Endpoints
The global, randomized, double-blind, placebo-controlled RINGSIDE study (NCT04871282) enrolled 156 patients, making it the largest randomized trial conducted in desmoid tumors. Patients received varegacestat 1.2 mg once daily or placebo until disease progression or death, with progression-free survival serving as the primary endpoint.
The treatment benefit was consistent across key subgroups, including tumor location, baseline tumor size, age, and prior systemic therapy exposure. Varegacestat also met all key secondary endpoints.
Confirmed objective response rate reached 56% compared with 9% for placebo, while median time to response was reduced to 8.2 months versus 16.7 months. Significant reductions in tumor volume were observed at week 24, supporting the therapy’s antitumor activity.
Beyond tumor control, varegacestat delivered meaningful symptom improvement. Patients experienced significant reductions in worst pain intensity, with a clinically meaningful benefit emerging as early as week 4 and maintained through week 12. Given the substantial pain burden associated with desmoid tumors, this finding may be particularly relevant in clinical practice.
Safety Profile and Class Consistency
Varegacestat demonstrated a manageable safety profile consistent with the gamma secretase inhibitor class. The most common adverse events included diarrhea, fatigue, rash, nausea, and cough, with 95% of events reported as grade 1 or 2.
Among premenopausal women, ovarian toxicity events were observed but were generally reversible, and no patients discontinued treatment because of these events. Long-term safety and durability of response continue to be assessed in the ongoing open-label extension phase.
Expert Perspective and Competitive Landscape
According to principal investigator Dr. Mrinal Gounder, the combination of durable progression-free survival, high response rates, tumor shrinkage, and rapid pain reduction supports varegacestat’s potential to become an important treatment option for patients with desmoid tumors.
The results position varegacestat alongside nirogacestat, the currently approved gamma secretase inhibitor in this setting, and could further expand treatment options for patients with progressive disease.
Regulatory Pathway and Global Outlook
The Phase 3 data support Immunome’s regulatory strategy. The company submitted a New Drug Application to the U.S. Food and Drug Administration in April 2026 and plans to file a Marketing Authorization Application with the European Medicines Agency by the end of the year.
If approved, varegacestat could provide a new treatment option for patients with progressing desmoid tumors, a rare disease that continues to carry substantial clinical burden despite recent therapeutic advances.
Reference
About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.