FDA Approves First Therapy for Rare Invasive Tumor Type With High Risk of Recurrence

In a phase 3 trial, none of the patients receiving nirogacestat reached median progression-free survival, indicating that it may effectively reduce disease progression.

The FDA has approved nirogacestat (Ogsiveo; SpringWorks Therapeutics) for the treatment of progressing desmoid tumors in adult patients who require systemic treatment, according to a press release. The approval is based on significant efficacy results from the phase 3 DeFi trial (NCT03785964), which were published in the New England Journal of Medicine.

“Desmoid tumors can have a significant impact on people’s lives and are difficult to manage due to their invasive nature and high rates of recurrence,” said study investigator Mrinal M. Gounder, MD, a sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center, in the press release.

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Desmoid tumors are rare and aggressive locally invasive tumors of the soft tissues. These tumors are more likely to affect patients of a younger age (between 20 to 44 years), and females may have a 3-times higher risk of having a desmoid tumor. The recurrence rate after surgical resection is 77%, so treatment guidelines have determined that systemic therapies should be a first-line intervention.

“This community has been waiting for an effective treatment that not only shrinks their tumors but also significantly improves pain, which is the most debilitating symptom reported by people living with desmoid tumors,” said Saqib Islam, CEO of SpringWorks, in the press release.

Despite the risk of recurrence associated with the disease, nirogacestat significantly reduced risk of disease progression by 71% (HR 0.29 (95% CI: 0.15, 0.55); p< 0.001), according to investigators. In fact, no patients in the nirogacestat group experienced disease progression or death, whereas median progression-free survival (PFS) in the placebo group was 15.1 months.

Further, the confirmed objective response rate (ORR) with nirogacestat was 41% versus 8% with placebo (p<0.001). Investigators also observed that complete response rate (CRR) in the nirogacestat arm was 7%. Nirogacestat also reduced median time to first response more than placebo (5.6 months and 11.1 months, respectively).

About the Trial

Trial Name: Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (DeFi)

ClinicalTrial.gov ID: NCT03785964

Sponsor: SpringWorks Therapeutics, Inc.

Estimated Completion Date: December 31, 2023

Based on clinical trial data, the oral gamma secretase inhibitor is deemed safe and tolerable. Adverse events experienced by 15% or more of patients included diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and/or dyspnea.

Nirogacestat is beneficial for PFS and ORR regardless of patient sex, tumor location, tumor focality, patient treatment status or treatment history, mutational status, or family disease history, according to findings from DeFi. In addition, it was shown to improve pain, quality of life, and other patient reported outcomes (PROs).

“It was encouraging to see in the DeFi trial that [nirogacestat] achieved statistically significant and clinically meaningful improvements across the primary and all key secondary endpoints, while also having a manageable safety profile,” Gounder said in the press release. “This approval represents an important therapeutic advance for patients.”

Reference

SpringWorks Therapeutics Announces FDA Approval of OGSIVEO™ (nirogacestat) as the First and Only Treatment for Adults with Desmoid Tumors. SpringWorks Therapeutics. News Release. November 28, 2023. Accessed on November 28, 2023. https://ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-announces-fda-approval-ogsiveotm