A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)

NCT ID: NCT07170644

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-08
• Study Completion Date: 2030-12-31

Brief Summary

This study is being conducted to characterize the efficacy and safety of nirogacestat in Japanese adults with progressing desmoid tumors/aggressive fibromatosis.

Detailed Description

Desmoid tumors, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumors. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and occasionally mortality in patients.

Nirogacestat is a tumor inhibitor that works by slowing or stopping the growth of tumor cells. Nirogacestat is a tablet taken by mouth and has been approved in the USA for adult patients with progressing desmoid tumors who require systemic treatment.

This is an open-label study to characterize the efficacy and safety of nirogacestat in Japanese adults with progressing desmoid tumors/aggressive fibromatosis (DT).

Conditions

Desmoid Tumor; Aggressive Fibromatosis

Keywords

Nirogacestat; PF-03084014; GSI; gamma secretase inhibitor; notch pathway; Ogsiveo

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nirogacestat

Nirogacestat 150 mg by mouth, twice daily

Group Type: EXPERIMENTAL

Nirogacestat oral tablet

Intervention Type: DRUG

Nirogacestat tablet

Interventions

Nirogacestat oral tablet

Nirogacestat tablet

Intervention Type: DRUG

Other Intervention Names

PF-03084014; Ogsiveo

Eligibility Criteria

Inclusion Criteria

• Participant is aged ≥18 at the time of signing the informed consent.
• Participant has histologically confirmed DT (by local pathologist prior to informed consent) that has progressed by ≥20% as measured by RECIST v1.1 within 12 months of the screening visit scan.
• Participant has:

1. Treatment-naive, measurably progressing DT that is deemed not amenable to surgery without the risk of significant morbidity; OR

2. Recurrent, measurably progressing DT following at least 1 line of therapy; OR

3. Refractory, measurably progressing DT following at least 1 line of therapy.

• Participant agreed to provide archival or new tumor tissue for re-confirmation of disease.
• Participant has a DT tumor where continued PD will not result in immediate significant risk to the participant.
• Participants who are receiving chronic NSAIDs as treatment for conditions other than DT must be receiving them prior to documented DT progressive disease (inclusion criterion 2) and on a stable dose for at least 28 days prior to the first dose of study treatment.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
• Participant has adequate organ and bone marrow function

Exclusion Criteria

• Participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat.
• Participant has experienced any of the following within 6 months of signing informed consent: clinically significant cardiac disease (New York Heart Association Class III or IV), myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
• Participant has had lymphoma, leukemia, or any malignancy within the past 5 years at the time of informed consent, except for any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast), with no evidence of metastatic disease for 3 years at the time of informed consent.
• Participant has known severe hepatic impairment
• Participant previously received or is currently receiving gamma secretase inhibitors or anti-Notch antibody therapy
• Participant is currently using any treatment for DT/AF including tyrosine kinase inhibitors (TKIs) or any investigational treatment 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment
• Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 (CYP) 3A4 inhibitors, or strong CYP3A inducers within 14 days prior to the first dose of study treatment.
• Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year of signing informed consent.
• Participant is unable to comply with study related procedures (including, but not limited to, the completion of electronic patient-reported outcomes)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SpringWorks Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Nagoya University Hospital

Nagoya, Aichi-ken, Japan

Site Status: RECRUITING

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

Site Status: RECRUITING

Osaka Prefectural Hospital Organization Osaka International Cancer Institute

Osaka, , Japan

Site Status: RECRUITING

Countries

Japan

Central Contacts

Nicole H Leedom

Role: CONTACT

Phone: 984-204-8065

Email: clinical@springworkstx.com

Other Identifiers

NIR-DT-202

Identifier Type: -

Identifier Source: org_study_id