(P 188) IMPACT OF NIROGACESTAT ON FUNCTIONAL STATUS IN PATIENTS WITH DESMOID TUMORS: RESULTS FROM THE PHASE 3 DEFI STUDY

Objective: Patients with desmoid tumors (aggressive fibromatosis) can experience severe pain and functional impairment (e.g., difficulty walking, using the toilet, and lifting heavy objects); in addition, symptoms can negatively affect work, school, and relationships with friends or family. In the phase 3 DeFi trial of adult patients with progressing desmoid tumors, nirogacestat (n=70) demonstrated statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (HR: 0.29 [95% CI, 0.15–0.55]; p< 0.001) and in all key secondary efficacy endpoints (p < 0.01) compared with placebo (n=72). Secondary and exploratory DeFi endpoints included different aspects of patient-reported functional status to further characterize nirogacestat’s treatment effect.

Methods: In DeFi, patients completed prespecified functional status assessment tools at baseline and at each 28-day cycle during the first year of treatment: the GOunder/Desmoid Tumor Research Foundation DEsmoid Impact Scale (GODDESS-DTIS) Physical Functioning domain (moving, reaching, vigorous activity, moderate activity, accomplishing less; 7-day recall); the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) Physical Functioning (strenuous activities, taking a long walk, taking a short walk, need to stay in a bed or chair, help with eating/dressing/washing/using the toilet; 7-day recall) and Role Functioning (work/other daily activities, hobbies/leisure activities; 7-day recall) domains; and the Patient-Reported Outcomes Measurement Information System Physical Function Short Form 10a (PROMIS PF10a; dexterity/upper extremities, walking/mobility/lower extremities, neck/back, daily activities such as errands; 7-day recall). Changes from baseline in functional status scores were compared between nirogacestat and placebo at cycle 10 using a mixed model with repeated measures (MMRM). Cycle 10 was preselected to allow adequate time for a treatment effect to be observed.

Results: Statistically significant improvements from baseline in physical and role functioning were observed with nirogacestat compared with placebo at cycle 10 across all assessment tools (Table). Differences between the nirogacestat and placebo groups emerged as early as cycle 3 for some aspects of patient-reported functional status.

Conclusion: Significantly greater improvement in different aspects of functional status was observed with nirogacestat compared with placebo across multiple assessment tools in adult patients with desmoid tumors. Because patients with desmoid tumors can experience substantial functional impairment, improvement of functional status is an important treatment goal.