Ogsiveo (Nirogacestat) Shows Sustained Efficacy in Desmoid Tumors: Long-Term Phase 3 Data
Key Insights
Long-term data from the Phase 3 DeFi trial demonstrates continued tumor size reduction with Ogsiveo (nirogacestat) in adult patients with desmoid tumors (search).
The study showed an increased objective response rate (ORR) with additional complete responses (CRs) observed over a median treatment duration of approximately 3 years.
Patients experienced sustained improvements in desmoid tumor symptoms, including pain and physical functioning, with a consistent safety profile throughout the extended treatment period.
SpringWorks Therapeutics announced updated long-term efficacy and safety data from the Phase 3 DeFi trial of Ogsiveo (nirogacestat) in adult patients with progressing desmoid tumors (search). The data, presented at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting, highlight the sustained benefits of nirogacestat with extended treatment duration.
The DeFi trial initially randomized 142 patients to either nirogacestat (150 mg twice daily) or placebo. The primary analysis, with a data cutoff in April 2022, demonstrated statistically significant improvements in progression-free survival (PFS) and objective response rate (ORR) for nirogacestat compared to placebo. The updated analysis, with a data cutoff in August 2024, reflects a median nirogacestat treatment duration of 33.6 months.
Sustained Tumor Reduction and Improved Response Rates
Longer-term treatment with nirogacestat led to further reductions in tumor size. The median best percent reduction from baseline in target tumor size was -32.3% at year one (n=46) and -75.8% for patients completing at least four years (n=15) of treatment. The objective response rate (ORR) increased to 45.7% (34.3% partial response, 11.4% complete response), with three new partial responses (PRs) and three new complete responses (CRs) reported since the April 2022 data cutoff.
Consistent Symptom Relief and Safety Profile
Patients treated with nirogacestat experienced early and sustained improvements in pain, desmoid tumor-specific symptom severity, and physical functioning. These improvements were maintained for up to 45 months of treatment. The most frequently reported treatment-emergent adverse events (TEAEs) included diarrhea, nausea, fatigue, hypophosphatemia, and headache. The incidence and severity of these events generally decreased over time.
Efficacy Across Prognostic Subgroups
A post-hoc analysis of the DeFi trial assessed the effect of nirogacestat in subgroups of patients with poor prognostic factors, including larger tumor size (>10 cm), younger age (≤30 years), specific CTNNB1 (search) gene mutations, and presence of pain at baseline. The results showed that nirogacestat led to consistent improvements in PFS, ORR, and patient-reported outcomes (PROs) versus placebo, regardless of the subgroup. The ORR risk difference between nirogacestat and placebo ranged from 18.1% to 56.0%, favoring nirogacestat.
Insights into CTNNB1 and APC Mutations
A poster presentation at CTOS detailed an analysis of patients with desmoid tumors (search) and co-occurring somatic mutations of CTNNB1 (search) and APC (search). Descriptive results suggest that patients with this mutational profile may benefit from nirogacestat treatment, although they may experience a delayed treatment response.
About Ogsiveo (Nirogacestat)
Ogsiveo (nirogacestat) is an oral, selective, small molecule gamma secretase inhibitor approved in the United States for the treatment of adult patients with progressing desmoid tumors (search) who require systemic treatment. Desmoid tumors are rare, locally invasive soft tissue tumors that can cause pain, functional limitations, and reduced quality of life.