Nirogacestat May Offer an Additional Treatment Option for Desmoid Tumors

Commentary
Video

Brian Van Tine, MD, PhD, also discusses how the treatment of desmoid tumors has evolved following data supporting the use of sorafenib in this population.

In an interview with CancerNetwork® during Sarcoma Awareness Month 2023, Brian Van Tine, MD, PhD, spoke about his work on the phase 3 DeFi study (NCT03785964) evaluating nirogacestat (Ogsiveo) in patients with desmoid tumors, and how this agent may expand treatment options for this population if it were to receive FDA approval.1

Van Tine, a professor of medicine in the Division of Oncology, Section of Medical Oncology at Washington University School of Medicine’s Siteman Cancer Center, also discussed how sorafenib (Nexavar) acted as a catalyst that led to the evolution of treatment for this patient population and even resulted in the publication of a National Comprehensive Cancer Network (NCCN) compendium listing for desmoid tumors.2

The FDA granted priority review to nirogacestat as a treatment for adult patients with desmoid tumors in February 2023.3

Transcript:

The treatment of desmoid [tumors] has actually been evolving rapidly since the phase 3 Alliance clinical trial [NCT02066181] that first reported the activity of sorafenib.4 And in that same study, we found out there was a 20% spontaneous regression rate of this tumor if you do nothing. Our understanding of this tumor has changed and evolved. We've done a lot of work in this area, and what's interesting is that we understand there's a β‐catenin mechanism, and nirogacestat gets into that signaling. And all of a sudden, not only do we have sorafenib as an NCCN compendium listing for the treatment of desmoid [tumors], but nirogacestat, which is hopefully coming out as an FDA-approved treatment for desmoid [tumors].

The data that came out in the [phase 3 DeFi] trial are reminiscent of that of sorafenib. The [adverse] effect profiles are different between the 2 agents, but having more than one drug for the desmoid population as this treatment paradigm evolves and we now treat these tumors more medically than surgically, having more than one option is good.

References

  1. Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med. 2023;388(10):898-912. doi:10.1056/NEJMoa2210140
  2. NCCN. Clinical Practice Guidelines in Oncology. Soft tissue sarcoma, version 2.2023. Accessed July 24, 2023. bit.ly/3Y58VTn
  3. SpringWorks Therapeutics announces FDA acceptance and priority review of new drug application for nirogacestat for the treatment of adults with desmoid tumors. News release. SpringWorks Therapeutics. February 27, 2023. Accessed February 27, 2023. bit.ly/3SxA1Qk
  4. Gounder MM, Mahoney MR, Van Tine BA, et al. Sorafenib for advanced and refractory desmoid tumors. N Engl J Med. 2018; 379:2417-2428. doi:10.1056/NEJMoa1805052
Recent Videos
Based on a patient’s SCLC subtype, and Schlafen 11 status, patients will be randomly assigned to receive durvalumab alone or with a targeted therapy in the S2409 PRISM trial.
Daniel Peters, MD, aims to reduce the toxicity associated with AML treatments while also improving therapeutic outcomes.
Numerous clinical trials vindicating the addition of immunotherapy to first-line chemotherapy in SCLC have emerged over the last several years.
Patients with AML will experience different toxicities based on the treatment they receive, whether it is intensive chemotherapy or targeted therapy.
A younger patient with AML who is more fit may be eligible for different treatments than an older patient with chronic medical conditions.
Breast cancer care providers make it a goal to manage the adverse effects that patients with breast cancer experience to minimize the burden of treatment.
Social workers and case managers may have access to institutional- or hospital-level grants that can reduce financial toxicity for patients undergoing cancer therapy.
Genetic backgrounds and ancestry may hold clues for better understanding pancreatic cancer, which may subsequently mitigate different disparities.
Factors like genetic mutations and smoking may represent red flags in pancreatic cancer detection, said Jose G. Trevino, II, MD, FACS.
Insurance and distance to a tertiary cancer center were 2 barriers to receiving high-quality breast cancer care, according to Rachel Greenup, MD, MPH.
Related Content
Data from a phase 1/2 trial demonstrate the potential anti-tumor activity of FOG-001 in patients with desmoid tumors.

FOG-001 Earns FDA Fast Track Designation in Desmoid Tumors

Russ Conroy
November 13th 2025
Article

Data from a phase 1/2 trial demonstrate the potential antitumor activity of FOG-001 in patients with desmoid tumors.

Experts discuss considerations for improving the care of patients with prostate, kidney, and bladder cancer in community-based practices at World GU 2025.

Episode 13: Perspectives on Optimizing Community Care at World GU 2025

Manojkumar Bupathi, MD, MS;Benjamin Garmezy, MD;Sam S. Chang MD, MBA;Jeff Yorio, MD
September 12th 2025
Podcast

Experts discuss considerations for improving the care of patients with prostate, kidney, and bladder cancer in community-based practices at World GU 2025.

ADCE-D01 Earns FDA Fast Track Designation in Soft Tissue Sarcoma | Image Credit: © David A Litman - stock.adobe.com.

ADCE-D01 Earns FDA Fast Track Designation in Soft Tissue Sarcoma

Russ Conroy
October 10th 2025
Article

Investigators are currently assessing ADCE-D01 among those with metastatic and/or unresectable soft tissue sarcoma in the phase 1/2 ADCElerate1 trial.

Geraldine O’Sullivan Coyne, MD, MRCPI, PhD, discusses how the START center may expand access to novel therapies for patients who reside in a community.

START Center Aims to Bring New Cancer Treatments, Trials to the Community

Geraldine O’Sullivan Coyne, MD, MRCPI, PhD
August 25th 2025
Podcast

Geraldine O’Sullivan Coyne, MD, PhD, MRCPI, discusses how the START center may expand access to novel therapies for patients who reside in a community setting.

Managing AEs with Gemcitabine Intravesical System in NMIBC

Managing AEs with Gemcitabine Intravesical System in NMIBC

Gary Steinberg, MD
September 20th 2025
Article

Gary Steinberg, MD, compared the AE profile of the gemcitabine intravesical system for BCG-unresponsive NMIBC with other intravesical therapies.

Experts discussed diagnosing and treating epithelioid sarcoma, emphasizing the importance of clinical history and the role of multiple multidisciplinary clinicians in care.

Diagnosing and Treating Patients With Epithelioid Sarcoma

ONCOLOGY Staff
July 4th 2025
Article

Experts discussed diagnosing and treating epithelioid sarcoma, emphasizing the importance of clinical history and the role of multiple multidisciplinary clinicians in care.