Presentation of additional data from phase III DeFi trial of nirogacestat in adults with desmoid tumors at the 2023 ASCO annual meeting.- Springworks Therapeutics.

“Pain is the most debilitating symptom reported by patients living with desmoid tumors and reducing this burden is a key treatment goal for physicians. We are pleased with the robust data observed using multiple assessment tools demonstrating clinically significant reductions in pain with nirogacestat treatment,” said Jim Cassidy, M.D., Ph.D., Chief Medical Officer of SpringWorks. “We are also encouraged by the substantial reductions in tumor volume and T2 hyperintensity seen in the DeFi study, which are consistent with the significant improvements in progression-free survival and objective response rate previously reported, and further elaborate on the activity profile of nirogacestat in desmoid tumors. We believe that nirogacestat has the potential to be a significant advance for patients and we look forward to our continued discussions with the FDA as they review our New Drug Application.”

Poster Presentations at the 2023 ASCO Annual Meeting: "Impact of nirogacestat on pain, a key symptom in patients with desmoid tumors (DT): results from the Phase III DeFi study (Poster #: 498)";Abstract #: 11564. Poster Session Date and Time: Saturday, June 3, 1:15 – 4:15 p.m. CT (2:15 – 5:15 p.m. ET).

As previously reported, in the DeFi trial (NCT03785964), nirogacestat met its primary endpoint of significantly improving progression-free survival compared to placebo in adult patients with progressing desmoid tumors (hazard ratio: 0.29 [95% CI, 0.15–0.55]; P<0.001). nirogacestat also achieved a significant and clinically meaningful reduction in pain severity, a key secondary endpoint, compared with placebo at cycle 10 (p><0.001). a manageable safety profile was observed with nirogacestat, with 95% of all treatment-emergent adverse events (teaes) reported as either grade 1 or 2. the most frequently reported teaes that occurred in participants receiving nirogacestat were diarrhea (84%), nausea (54%), fatigue (51%), hypophosphatemia (42%), and maculopapular rash (32%)..></0.001).></0.001).>

During the DeFi study, patients also completed three prespecified assessment tools that included pain measurements to characterize the impact of nirogacestat on this symptom. Changes from baseline in pain severity were compared between treatment arms at Cycle 10 per the prespecified exploratory endpoints. Statistically significant and clinically meaningful reductions in pain were observed with nirogacestat compared with placebo at Cycle 10 across all three assessment tools evaluated in DeFi: the Brief Pain Inventory-Short Form (BPI-SF), the GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom Scale (GODDESS-DTSS), and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30).

The following results from the assessment tools will be presented at ASCO : i. Nirogacestat significantly reduced pain severity per the BPI-SF “worst pain” score (0–10 range) by 1.55 points, compared with 0.05 points with placebo (P<0.001) at cycle 10. ii.nirogacestat significantly reduced pain per the goddess-dtss pain score (0–10 range) by 1.78 points, compared with an increase in pain of 0.34 points with placebo (p><0.001) at cycle 10. the goddess-dtss pain score includes questions about worst pain, dull pain, and shooting pain. iii. nirogacestat significantly reduced pain per the eortc qlq-c30 pain subscale (0–100 range) by 22.36 points, compared with an increase in pain of 7.00 points with placebo (p><0.001) at cycle 10. this pain sub-scale includes questions about pain and its interference with daily activities. iv. a statistically significant greater proportion of patients achieved a clinically meaningful pain reduction with nirogacestat treatment compared with placebo at cycle 10 per the bpi-sf “worst pain” score (p="0.001)" and the goddess-dtss pain score (p><0.001). v. reductions in pain were rapid, becoming evident as early as cycle 2 (the first post-treatment timepoint evaluated), and these reductions were sustained through to the end of the double-blind phase of the defi trial.></0.001).></0.001)></0.001)></0.001)>

“Many patients with desmoid tumors live with severe, chronic pain that significantly impacts their quality of life,” said Winette T.A. van der Graaf, M.D., Ph.D., Group Leader and Medical Oncologist, Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands and investigator in the DeFi trial. “It is very encouraging that nirogacestat demonstrated a rapid, sustained and consistent reduction in different aspects of pain during the trial, including worst pain, dull pain, shooting pain, and pain interference with people’s ability to perform daily activities.”

See: Gounder M et al. Nirogacestat, a Gamma-Secretase Inhibitor for Desmoid Tumors. N Engl J Med 2023; 388:898-912. doi: 10.1056/NEJMoa2210140