The FDA has granted approval to nirogacestat for the treatment of adult patients with desmoid tumors.1

Findings from the phase 3 DeFi trial support this approval as in the study, nirogacestat reduced the risk of disease progression or death by 71% compared with placebo among patients with desmoid tumors (HR, 0.29; 95% CI, 0.15-0.55; P < .001).2

This study is the first positive study for a gamma secretase inhibitor in any indication, and it's the largest and the most rigorous and robust clinical trial ever done in desmoid tumor, said Bernd Kasper, MD, PhD, professor, Mannheim University Medical Center, in an interview with Targeted Oncology. Nirogacestat demonstrated rapid, sustained and statistically significant improvements in all primary and secondary endpoints with a manageable safety profile. So it is definitely a candidate for register for registration in this indication. And it will probably be the standard of care for decimo to most in need of systemic therapy.

Among those given nirogacestat (n = 70), the Kaplan-Meier-estimated median PFS was not estimated and patients treated with placebo (n = 72) had a median PFS of 15.1 months (95% CI, 8.4-not estimable). The likelihood of being event-free at 1 year was higher among patients treated with nirogacestat vs placebo, at 85% (95% CI, 73%-92%) and 53% (95% CI, 40%-64%), respectively.

Additionally, event-free survival rates at 2 years were 76% (95% CI, 61%-87%) with nirogacestat and 44% (95% CI, 32%-56%) with placebo, respectively. The confirmed ORR was 41% with nirogacestat vs 8% with placebo (P < .001), and the complete response rates were 7% and 0%, respectively.

The median time to confirm first response was 5.6 months and 11.1 for the investigative vs control arm, respectively, and the median best percent change in target tumor size was -27.1% (range, -100 to 37) vs 2.3% (range, -100 to 47).

Any-grade adverse events (AEs) were observed in 100% of patients in the nirogacestat arm compared with 96% in the placebo arm, with grade 3 or greater AEs observed in 55% vs 17% of patients in the nirogacestat vs placebo arms, respectively.

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FDA Approves Nirogacestat for Patients With Desmoid Tumors - Targeted Oncology