STAMFORD, Conn.–(BUSINESS WIRE)–SpringWorks Therapeutics, a clinical-stage biopharmaceutical company
focused on developing life-changing medicines for patients with severe
rare diseases and cancer, today announced that the first patient has
been dosed in the Phase 3 “DeFi” (Desmoid/Fibromatosis)
trial evaluating nirogacestat, an oral, selective, small molecule
gamma-secretase inhibitor, in adult patients with progressing desmoid
tumors.
Desmoid tumors are rare and often debilitating and disfiguring
soft-tissue tumors that can aggressively invade surrounding healthy
tissues, including joints, muscles, blood vessels, nerves and internal
organs. Depending on their size and location, desmoid tumors can cause
significant morbidities, including severe pain, disfigurement, internal
bleeding, debilitating loss of range of motion, and, in rare cases,
desmoid tumors can be fatal.1 It is estimated that 1,000 to
1,500 new cases of desmoid tumors are diagnosed each year in the United
States.2,3 There are currently no therapies approved by the
U.S. Food and Drug Administration (FDA) for the treatment of desmoid
tumors.
“For patients living with these debilitating tumors, the DeFi trial
marks a meaningful step forward in what we hope will result in the first
approved treatment for this underserved patient community,” said Saqib
Islam, Chief Executive Officer of SpringWorks Therapeutics. “I am
grateful for the persistence of our partners, colleagues and the patient
advocacy community, whose collective efforts made it possible for
SpringWorks to advance nirogacestat into our Phase 3 DeFi trial. We look
forward to enrolling patients to confirm the clinical benefits of
nirogacestat for people with 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.
About the DeFi Trial
The DeFi trial is a global, randomized, double-blind, placebo-controlled
Phase 3 trial to evaluate the efficacy, safety and tolerability of
nirogacestat in adult patients with progressing desmoid tumors. The
study will enroll approximately 100 adult patients, who will receive 150
mg of nirogacestat or placebo twice daily. Key eligibility criteria
include tumor progression by ≥20% as measured by Response Evaluation
Criteria in Solid Tumors (RECIST 1.1) within 12 months prior to the
first dose of study treatment.
The primary endpoint is progression-free survival (PFS), defined as the
time from randomization until the date of assessment of progression or
death by any cause using RECIST 1.1. Secondary endpoints include safety
and tolerability measures, as well as overall response rate, tumor
volume changes as assessed by MRI, and changes in baseline in
patient-reported outcomes.
More information about the DeFi trial is available at www.clinicaltrials.gov
under the identifier NCT03785964.
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 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 and lower
extremities, abdominal walls, thoracic areas, and the 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, debilitating loss of range of motion,
and, in rare cases, desmoid tumors can be fatal.1
Desmoid tumors can affect children and adults, and are more commonly
diagnosed in young adults between 20-30 years of age, with a
two-to-three-fold predominance in females.1,4 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 per year in the United
States.2,3
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 observed.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. 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 been investigated in 24 patients with desmoid tumors
across Phase 1 and Phase 2 clinical trials. In these studies, treatment
with nirogacestat demonstrated 100% disease control rate as measured by
RECIST criteria, and median PFS was not reached by the time of
publication in either trial due to lack of tumor progression events.
Nirogacestat also showed an encouraging tolerability profile in these
earlier studies, with many patients remaining on treatment for years and
only one patient in the combined trials discontinuing due to an adverse
event. The most common adverse events in prior studies were diarrhea,
skin disorders and hypophosphatemia.
About SpringWorks Therapeutics
At SpringWorks Therapeutics, a clinical-stage biopharmaceutical company,
we are driven to develop life-changing medicines for patients with
severe rare diseases and cancer. Since our launch in 2017, we have
worked to identify and advance promising science, beginning with our
licensed clinical therapies from Pfizer Inc. We pioneer efficient
pathways for drug development, leveraging shared-value partnerships with
patient advocacy groups, innovators in industry and academia, and
investors so that together, we can unlock the potential of science and
bring new therapies to underserved patients. Nirogacestat, our gamma
secretase inhibitor for the treatment of desmoid tumors is currently in
a Phase 3 clinical trial, and SpringWorks Therapeutics expects to
initiate a Phase 2b study of PD-0325901, our MEK 1/2 inhibitor for
neurofibromatosis type 1 patients with plexiform neurofibromas, in the
third quarter of 2019. PD-0325901 also holds promise as the backbone for
combination therapies to treat metastatic solid tumors. At SpringWorks,
we ignite the power of promising science to unleash new possibilities
for patients. For more information, please visit www.springworkstx.com.
Follow SpringWorks Therapeutics on social media: @SpringWorksTx
and LinkedIn.
References
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 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
3 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
4 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
5 Scaramussa, F.S. & Castro, U. B. (2016). Desmoid Tumor in Hand: A Case
Report. SM Journal of Orthopedics, 2(3),1036.
Contacts
Kim Diamond
Vice President, Communications and Investor Relations
Phone:
646-661-1255
Email: kdiamond@springworkstx.com