MILAN, August 18, 2025 — A new era in desmoid tumor treatment is dawning. The European Commission recently approved nirogacestat, the first drug specifically designed to combat this rare cancer, and now, a Phase III clinical trial called Ringside has yielded promising results for a second potential treatment, varegacestat.
A Second Chance for Patients with Limited Options
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The Ringside study demonstrates a significant improvement in progression-free survival with varegacestat, offering hope for those facing this challenging diagnosis.
- Varegacestat significantly improved progression-free survival compared to placebo, reducing the risk of disease progression or death by 84%.
- The objective response rate was 56% with varegacestat, a substantial increase from the 9% seen in the placebo group.
- Patients receiving varegacestat experienced a median tumor volume reduction of 83%, while those on placebo saw an 11% increase.
- The drug was generally well-tolerated, suggesting a favorable safety profile.
For years, desmoid tumors—slow-growing, often painful masses—have been notoriously difficult to treat. Surgery, while sometimes necessary, can be disfiguring and doesn’t always prevent recurrence. Until recently, there were no medications specifically approved to target these tumors. Nirogacestat, a gamma-secretase inhibitor, changed that landscape, and now varegacestat is poised to potentially offer another valuable tool for clinicians.
How Does Varegacestat Work?
Developed by Immunome, varegacestat works by inhibiting gamma-secretase, an enzyme crucial for activating the Notch protein. This protein plays a key role in cell growth and development. In desmoid tumors, the Notch signaling pathway becomes disrupted, fueling uncontrolled tumor growth. By blocking gamma-secretase, varegacestat aims to restore balance and halt the proliferation of cancer cells.
“Due to their unpredictable nature and the limitations of current treatment options, desmoid tumors can have a devastating physical and emotional impact on patients,” explains Minal M. Angry, an oncologist specializing in sarcomas and drug development at the Memorial Sloan Kettering Cancer Center in the USA, and principal investigator of the Ringside study. The trial spanned 53 countries, including the United States, Australia, and Europe, with participation from centers in Milan, Bologna, and Rome, Italy. “In the trial, we were surprised by the benefits in terms of progression-free survival, the high response rate to therapy and the reduction in tumor volume obtained with varegacestat.”
Ringside Study Details
The Ringside study involved 156 adults diagnosed with desmoid tumors. Participants were randomly assigned to receive either varegacestat or a placebo until their disease progressed or they died. The study’s primary goal—to assess progression-free survival—was decisively met. Varegacestat demonstrated a statistically significant and clinically relevant improvement in PFS compared to placebo.
Beyond progression-free survival, the study revealed impressive results in other areas. The objective response rate (ORR) reached 56% with varegacestat, compared to just 9% with the placebo. Furthermore, patients on varegacestat experienced a median reduction in tumor volume of 83%, while those receiving the placebo saw an 11% increase. The study also confirmed improvements in reducing tumor volume and pain intensity, with the drug proving generally well-tolerated.
“The results of the Ringside trial demonstrate the therapeutic potential of varegacestat, a once-daily oral medicine that can help desmoid tumor patients take back their lives,” said Clay Siegall, CEO of Immunome, which plans to submit an application for drug approval to the US Food and Drug Administration (FDA) in the second quarter of 2026.
