Tumor volume and T2 hyperintensity changes from DeFi: A phase 3, randomized, controlled trial of nirogacestat in patients with desmoid tumors.

• DOI: 10.1200/jco.2023.41.16_suppl.11514
• Publication Date: 2023-06-04T16:31:33Z
• Authors: Thierry Alcindor; Bernd Kasper; Mrinal M. Gounder; Ravin Ratan; Winette T.A. Van ...; Breelyn A. Wilky; Richard F. Riedel; Noah Federman; Agnese Peruzzi; Stephanie Moody; Allison Lim; Brad Tumminello; Shivaani Kummar; Patrick Schöffski
• Keywords: Clinical endpoint; Surrogate endpoint

11514 Background: MRI tumor volume or T2 signal intensity changes may represent novel imaging techniques that could have a prognostic predictive value for assessing response in desmoid tumors (DT). For example, hyperintense areas on T2-weighted images been associated with active fibroblastic proliferation and ≥90% hyperintensity is DT disease progression, whereas iso- hypo-intense are inactive sites of disease. In DeFi (NCT03785964), the gamma secretase inhibitor nirogacestat (n=70 patients) significantly improved primary endpoint PFS compared placebo (n=72 patients; hazard ratio, 0.29 [95% CI, 0.15, 0.55; P<0.001]) secondary ORR per blinded, independent central review (41% vs 8%; P<0.001). Complete responses were achieved 7% 0% placebo. Here, we present an exploratory analysis DeFi. Methods: Eligible adults had histologically confirmed progressed ≥20% RECIST v1.1 within 12 months screening. Patients randomized 1:1 to receive 150 mg twice daily taken continuously 28-day cycles. Volumetric largest target evaluated at screening every 6 cycles during double-blind phase. represented as ratio total muscle background. A independent, radiologist reviewed all scans. Results: Nirogacestat treatment led more substantial reductions versus (Table). At baseline, similar proportions patients each arm (95% 97%). This changed from baseline <90% any time after 34% 15% those Conclusions: DeFi, demonstrated reduction by DT. These results consistent significant improvement nirogacestat. data suggest volumetric might provide additional information evaluation The these should be further studied. Clinical trial information: NCT03785964 . [Table: see text]