Bernd Kasper, MD, PhD, University of Heidelberg Cancer Center, discusses results from the DeFi clinical trial of nirogacestat in patients with desmoid tumors.
Desmoid tumors are abnormal growths that arise from connective tissue. The tumors can occur anywhere in the body and are fibrous, much like scar tissue. They are generally not considered malignant because they do not metastasize, however, they can aggressively invade the surrounding tissue and can be very difficult to remove surgically. These tumors often recur, even after apparently complete removal. The most common symptom of desmoid tumors is pain. Other signs and symptoms, depending on the size and location of the tumor, may include constipation, limping, or difficulty moving the arms or legs.
The DeFi clinical trial (NCT03785964) is a phase 3 global, randomized, multicenter, double-blind, placebo-controlled trial evaluating the efficacy, safety, and tolerability of nirogacestat in adult patients with progressing desmoid tumors. Nirogacestat is an oral, selective, small molecule gamma secretase inhibitor approved by the U.S. Food and Drug Adminsitration (FDA) as monotherapy for the treatment of adults with progressing desmoid tumors. Long-term safety and efficacy data from the DeFi clinical trial was recently published in the Journal of Clinical Oncology.
With a data cutoff date of December 2024, new results showed that median best percent reduction from baseline in target tumor size with continuous nirogacestat treatment was -32.3% at year 1 and -75.8% for patients completing at least 4 years of treatment. Objective response rate increased from 34.3% in year 1 to 45.7% in patients who received nirogacestat for up to 4 years. There were also three additional partial responses since the primary analysis, yielding 24 partial responses and 8 complete responses in total.
Improvements in patient-reported outcomes of pain, desmoid tumor-specific symptom severity and physical functioning, and global health status/quality of life and role functioning occurred early and were sustained up to 45 months of treatment. Overall, the incidence and severity of frequently reported treatment-emergent adverse events decreased through years two, three, and four of treatment. The most common adverse events were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
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