SpringWorks Therapeutics Announces Full Enrollment of Phase 3 DeFi Trial Evaluating Nirogacestat in Adult Patients with Desmoid Tumors - Seite 2

About Desmoid Tumors

Desmoid tumors, also referred to as aggressive fibromatosis or desmoid-type fibromatosis, are rare and often debilitating and disfiguring soft tissue tumors characterized by a growth pattern that can invade surrounding healthy tissues, including joints, muscle and viscera. While they can arise in any part of the body, the most common sites are the upper and lower extremities, abdominal wall, thoracic areas, and the head and neck. The severity of a desmoid tumor can vary based on the location of the tumor and the aggressiveness of its growth pattern. Desmoid tumors can cause significant morbidities, including severe pain, internal bleeding, incapacitating loss of range of motion, and, in rare cases, death.¹

Desmoid tumors typically occur in patients between the ages of 15 to 60 years, and are more commonly diagnosed in young adults between 30-40 years of age, with a two-to-three times higher prevalence in females.^1,2 It is estimated that there are 1,000 to 1,500 new cases diagnosed per year in the United States.^3,4

Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery.⁵ There are currently no FDA-approved therapies for the treatment of desmoid tumors.

About Nirogacestat

Nirogacestat is an investigational, oral, selective, small molecule gamma-secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.

In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the soluble BCMA from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA, which may serve as a decoy receptor for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is pursuing a combination therapy approach to evaluate nirogacestat as a BCMA potentiator across modalities by collaborating with industry leaders. To date, SpringWorks has entered into two clinical collaborations to evaluate nirogacestat in combination with GSK’s BCMA antibody-drug conjugate belantamab mafodotin and with Allogene’s allogeneic BCMA CAR-T cell therapy ALLO-715.