Desmoid tumors (DTs), 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 aggressively invade surrounding healthy tissues, including joints, muscles, blood vessels, nerves and internal organs. While they can arise in any part of the body, the most common sites are the upper extremities (arm, forearm, and hand), lower extremities (girdle, thigh, leg, and foot), abdominal wall, thoracic areas, and head and neck. The severity of desmoid tumors and associated symptoms varies based on their size, location, and the aggressiveness of the growth pattern. Desmoid tumors can cause significant morbidities, including severe pain, disfigurement, internal bleeding, and debilitating loss of range of motion, and, in rare cases, desmoid tumors can be fatal.1
Desmoid tumors affect both children and adults, are most commonly diagnosed in young adults between 20-30 years of age, with a two-to-three-fold predominance in females.1,2 It is estimated that desmoid tumors affect 2 to 5 per million people worldwide, and that there are 1,000 to 1,500 new cases diagnosed each year in the United States.3,4 Historically, desmoid tumors were treated with surgical resection or, in severe cases, amputation, but even with these interventions, high rates of tumor regrowth have been documented.5 There are no therapies currently approved for the treatment of desmoid tumors.
Our Investigational Therapy
Nirogacestat is an investigational oral, small molecule, gamma-secretase inhibitor that has been investigated in 24 patients with desmoid tumors across Phase 1 and Phase 2 clinical trials. SpringWorks is enrolling patients in the “DeFi” (Desmoid/Fibromatosis) trial, a Phase 3, double-blind, randomized, placebo-controlled, global clinical trial in adults with progressing desmoid tumors.
In June 2018, the FDA granted Orphan Drug designation for nirogacestat for the treatment of desmoid tumors and in November 2018 the FDA granted Fast Track designation for nirogacestat for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.
The mission of The Desmoid Tumor Research Foundation is to aggressively fund research to accelerate the development of improved therapies, and ultimately find a cure for desmoid tumors. The foundation collaborates with dedicated researchers and clinicians worldwide to improve the lives of patients through education, awareness, and support.
1 Gounder, M. M., Thomas, D. M., & Tap, W. D. (2017). Locally Aggressive Connective Tissue Tumors. Journal of Clinical Oncology, 36(2), 202-209. doi:10.1200/JCO.2017.75.8482.
2 Skubitz, K. M. (2017). Biology and Treatment of Aggressive Fibromatosis or Desmoid Tumor. Mayo Clinic Proceedings, 92(6), 947-964. doi:10.1016/j.mayocp.2017.02.012
3 Reitamo, J J; Häyry, P; Nykyri, E; Saxén, E. (1982). The desmoid tumor. I. Incidence, sex-, age- and anatomical distribution in the Finnish population. American Journal of Clinical Pathology, 77(6), 665-673. doi: 10.1093/AJCP.77.6.665
4 van Broekhoven, D. L., Grünhagen, D. J., den Bakker, M. A., van Dalen, T., & Verhoef, C. (2015). Time trends in the incidence and treatment of extra-abdominal and abdominal aggressive fibromatosis: a population-based study. Annals of surgical oncology, 22(9), 2817–2823. doi:10.1245/s10434-015-4632-y
5 Scaramussa, F.S. & Castro, U. B. (2016). Desmoid Tumor in Hand: A Case Report. SM Journal of Orthopedics, 2(3),1036.