RINGSIDE Phase II Study of Varegacestat for Treatment of Desmoid Tumors: A Randomized Dose-Finding Clinical Trial.
Rashmi Chugh, Arun Singh, Vladimir Andelkovic et al.
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In 30 seconds
RINGSIDE was an open-label, randomized, multicenter phase II dose-finding trial of oral varegacestat in adults with histologically confirmed, progressing desmoid tumors. Forty-two participants were assigned to one of three dose regimens, with safety as the primary endpoint and tumor-volume change at week 16 as a secondary endpoint. Treatment-related adverse events were reported by 41 (97.6%) participants; none were serious or grade 4/5. The 1.2-mg once-daily group had the greatest median tumor-volume reduction at week 16 (-51.91%) and a confirmed objective response rate of 35.7%.
Key findings
- At week 16, median tumor-volume change was -51.91% with 1.2 mg once daily, -15.25% with 2-mg intermittent dosing, and -9.50% with 4-mg intermittent dosing.
- Confirmed objective response rates were 35.7%, 21.4%, and 21.4%, respectively, across the three randomized dose groups.
- Treatment-related adverse events occurred in 41 (97.6%) participants; 9 (21.4%) had grade 3 events, with no serious or grade 4/5 events.
- Among 29 participants entering the extension on 1.2 mg once daily, confirmed objective response rate increased to 57.1%.
Why it matters
Progressing desmoid tumors can be locally aggressive, and effective treatment options are limited. This dose-finding trial provides evidence of tumor-volume reduction and objective responses with varegacestat, particularly with once-daily dosing, while describing the associated adverse-event profile. The findings help characterize a potential treatment approach but require interpretation in light of the phase II design.
What to keep in mind
The randomized trial included 42 participants, with 14 per dose arm, and was open-label. The extension findings came from participants who entered the extension and are not a randomized comparison.