RARE Daily

SpringWorks Reports Positive Results in Phase 3 Study in Adults with Progressing Rare Tumors

May 24, 2022

SpringWorks Therapeutics reported that a phase 3 study of its experimental therapy nirogascestat in adults with progressing desmoid tumors met its primary and secondary endpoints.

Photo: Saqib Islam, CEO of SpringWorks

Desmoid tumors are rare, aggressive, locally invasive, and potentially morbid tumors of the soft tissues. While they do not metastasize, desmoid tumors are associated with a high rate of recurrence. Sometimes referred to as aggressive fibromatosis, or desmoid fibromatosis, these soft tissue tumors can be serious, debilitating, and, in rare cases when vital organs are impacted, they can be life-threatening. Historically, desmoid tumors were treated with surgical resection, but this approach has become less favored due to a high recurrence rate after surgery. There are currently no FDA-approved therapies for the treatment of desmoid tumors.

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.

Nirogacestat has received Orphan Drug designation from the FDA for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.

The DeFi trial, a double-blind, placebo-controlled phase 3 trial met its primary endpoint of improving progression-free survival (PFS), demonstrating a statistically significant improvement for nirogacestat over placebo, with a 71 percent reduction in the risk of disease progression. In addition, the trial met all key secondary endpoints, with nirogacestat demonstrating statistically significant improvements as compared to placebo in objective response rate (ORR) and patient-reported outcomes (PROs).

Nirogacestat was generally well tolerated with a manageable safety profile. The majority of women of childbearing potential had adverse events consistent with ovarian dysfunction. Other adverse events were generally consistent with previously reported data.

Additional data are expected to be presented at an upcoming medical conference in the second half of 2022 and SpringWorks plans to submit a New Drug Application to the U.S. Food and Drug Administration in the second half of 2022.

“Desmoid tumors are aggressive soft-tissue tumors that can lead to severe negative outcomes for patients, including long-lasting pain, disfigurement, and amputation. In rare cases, when vital organs are impacted, desmoid tumors can also be life-threatening,” said Saqib Islam, CEO of SpringWorks. “Today’s announcement represents a significant milestone towards our goal of bringing the first approved therapy to the desmoid tumor community.”

Author: Rare Daily Staff

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