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

NCT07170644 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: NIR-DT-202
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Desmoid Tumor; Aggressive Fibromatosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  Objective response rate (ORR), defined as the proportion of participants with confirmed complete response (CR) + partial response (PR) assessed by independent Central Imaging Review using RECIST v1.1 (Eisenhauer 2009).

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 3 years.

Secondary Outcomes (6)

• Duration of response (DoR)

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 3 years.

• Time to Response (TTR)

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 3 years.

• Safety endpoints will include incidence of treatment-emergent adverse events (TEAEs), changes in laboratory parameters, vital signs, physical examination findings, and ECGs.

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 5 years.

• Progression Free Survival (PFS)

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 3 years.

• Symptoms and impacts will be assessed by evaluating change from baseline at Cycle 10 on the following patient reported outcomes (PROs):

  On the first day of every 3 cycles (each cycle is 28 days) until disease progression is observed or death, assessed up to approximately 3 years.

Study Arms (1)

Nirogacestat

EXPERIMENTAL

Nirogacestat 150 mg by mouth, twice daily

Drug: Nirogacestat oral tablet

Interventions

Nirogacestat oral tablet DRUG

Nirogacestat tablet

Also known as: PF-03084014, Ogsiveo

Nirogacestat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Treatment-naive, measurably progressing DT that is deemed not amenable to surgery without the risk of significant morbidity; OR
• Recurrent, measurably progressing DT following at least 1 line of therapy; OR
• 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.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
• Participant has adequate organ and bone marrow function

You may not qualify if:

• 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)

Sponsors & Collaborators

• SpringWorks Therapeutics, Inc.: lead

Study Sites (3)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

Osaka Prefectural Hospital Organization Osaka International Cancer Institute

Osaka, 541-8567, Japan

Location

MeSH Terms

Conditions

Desmoid Tumors

Interventions

nirogacestat

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: September 12, 2025
• Study Start: August 8, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): October 31, 2029
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

JP (3)