• Long-term continuous OGSIVEO treatment for up to 4 years was associated with further tumor size reductions, increase in objective response rate, sustained improvement in desmoid tumor symptoms and consistent safety profile.

Merck, a leading science and technology company, announced  that long-term efficacy and safety data from the Phase 3 DeFi trial of OGSIVEO® (nirogacestat), an oral gamma secretase inhibitor for the treatment of adults with progressing desmoid tumors who require systemic treatment, were published in the Journal of Clinical Oncology (JCO). The long-term follow-up data from DeFi, which was a global, randomized, multicenter, double-blind, placebo-controlled trial, were previously presented at the 2024 Connective Tissue Oncology Society Meeting. The new results published in JCO utilized a December 2024 data cutoff date (the final data cut of the clinical trial) and showed that longer-term treatment with OGSIVEO was associated with further reductions in tumor size, an increase in objective response rate (ORR) with additional partial responses (PRs) and complete responses (CRs), sustained improvement in patient reported outcomes, and a consistent safety profile compared to the April 2022 data cut off utilized for the primary analysis of the trial.

“Desmoid tumors are locally aggressive and complex tumors whose unpredictable growth can cause significant pain, functional impairment, and emotional distress. For many patients, these tumors disrupt daily life in ways that are often underestimated, so advancing treatment options that offer durable symptom relief and tumor control can make a meaningful difference for patients,” said Ravin Ratan, M.D., M.Ed., Associate Professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston and lead author of the JCO publication. “While the optimal duration of therapy may vary for many patients, the new data published in the JCO provide physicians with additional information regarding the long-term safety and efficacy of nirogacestat, and will help inform treatment decisions and improve patient care.”

In the Phase 3 DeFi trial primary analysis, which was previously published in the New England Journal of Medicine, OGSIVEO showed significant improvement versus placebo in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PRO) in adult patients with progressing desmoid tumors (DT; median [range] exposure: 20.6 [0.3-33.6] months).1 In the JCO publication, long-term efficacy and safety were evaluated in patients randomized to OGSIVEO and followed through the final data-cutoff date of December 2024. The median duration of OGSIVEO treatment in these patients was 33.6 (0.3 to 61.8) months.

Objective response rates (ORR) improved with long-term OGSIVEO treatment. While ORR was 34.3% (n = 24) in year 1, it increased to 45.7% (n = 32) in patients who received OGSIVEO for up to 4 years, with three additional complete responses (CRs) and three additional partial responses (PRs) since the primary analysis and yielding 24 (34.3%) PRs and 8 (11.4%) CRs in total. The median best percent reduction from baseline in target tumor size by RECIST 1.1 with continuous OGSIVEO treatment was −32.3% at year one (n=46) and −75.8% (n=15) for patients completing at least four years of treatment. Improvements in patient-reported outcomes (PROs) of pain, desmoid tumor-specific symptom severity, desmoid tumor-specific physical functioning, global health status/quality of life and role functioning occurred early (as early as Cycle 2, the first post-treatment timepoint evaluated as disclosed at the primary analysis) and were sustained with up to 45 months of treatment with OGSIVEO.

Overall, the incidence and severity of frequently reported treatment emergent adverse events (TEAEs) decreased through years two, three and four of treatment. The most common adverse events (>15%) reported in patients receiving OGSIVEO were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Please see Important Safety Information below, including Warnings & Precautions relating to diarrhea, ovarian toxicity, hepatotoxicity, non-melanoma skin cancers, electrolyte abnormalities, and embryo-fetal toxicity.²

“We are pleased that long-term continuous nirogacestat treatment for up to four years was associated with additional late responses and further tumor size reductions,” said Uche Iloeje, M.D., Senior Vice President, Global Head of Medical Affairs at SpringWorks Therapeutics. “These data represent the largest prospective analysis from a randomized controlled clinical trial of long-term exposure to any systemic agent for desmoid tumors and provide valuable insights on the benefits of OGSIVEO for patients with desmoid tumors.”