Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03785964 | Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) | PHASE3 | COMPLETED | 142 | — | — | Apr 17, 2019 | Oct 17, 2024 | Jan 31, 2025 | 52 | United States, Belgium +5 |
| NCT07170644 | A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF) | PHASE2 | ACTIVE NOT_RECRUITING | 20 | — | — | Aug 8, 2025 | Oct 31, 2029 | May 8, 2026 | 3 | Japan |
| NCT05949099 | Study of Cryoablation and Nirogacestat for Desmoid Tumor | PHASE2 | RECRUITING | 28 | — | — | Aug 15, 2023 | Feb 1, 2028 | Sep 8, 2025 | 1 | United States |
Progression will be determined radiographically using RECIST v1.1 (Eisenhauer, 2009) or clinically as assessed by the investigator. Clinical progression is defined as the onset or worsening of symptoms resulting in a global deterioration of health status causing the permanent discontinuation from study treatment and the initiation of emergent treatment (e.g., radiotherapy, surgery, or systemic therapy including chemotherapy or tyrosine kinase inhibitors) for DT/AF. Events of clinical progression will be adjudicated by an independent blinded central Endpoint Adjudication Committee (EAC) which will qualify events of clinical progression for inclusion in the PFS endpoint prior to study unblinding according to an EAC Review Charter.
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).
Clinical benefit (CB) is defined as the number of participants assessed with a complete response (CR), partial response (PR), or stable disease (SD) within 1 year and with no evidence of loss of response nor progression within that year. Response \& progression will be assessed according to the Revised Response Evaluation Criteria in Solid Tumors (RECIST)v1.1, as follows: RECIST v1.1: * CR=Disappearance of all lesions * PR=≥30% decrease in diameter of target lesions * Progressive disease (PD)=20% increase in diameter of target lesion; progression of non-target lesion; or ≥1 new lesion(s) For the overall outcome: * SD=Changes not meeting above criteria * Overall Response (OR)=CR+PR * CB=CR+PR+SD
| Arm | Type | Description |
|---|---|---|
| Double-Blind Phase - Nirogacestat | EXPERIMENTAL | Nirogacestat 150 mg by mouth, twice daily |
| Double-Blind Phase - Placebo | PLACEBO_COMPARATOR | Placebo by mouth, twice daily |
| Open-Label Phase - Nirogacestat | EXPERIMENTAL | Nirogacestat 150 mg by mouth, twice daily |
| Nirogacestat | EXPERIMENTAL | Nirogacestat 150 mg by mouth, twice daily |
| Nirogacestat 150 mg | EXPERIMENTAL | Patients will receive 3-cycle lead-in with systemic therapy with nirogacestat 150 mg po BID, given continuously. |
| Name | Type | Description |
|---|---|---|
| Nirogacestat oral tablet | DRUG | Nirogacestat tablet |
| Placebo Oral Tablet | DRUG | Sugar pill manufactured to mimic nirogacestat 50 mg tablet |
| Nirogacestat | DRUG | Nirogacestat 150 mg by mouth twice-daily continuously for Cycles 1 through 3. Treatment with nirogacestat may continue via this study protocol for up to 24 months (26 cycles of treatment), unless there is progression of disease, intolerance, start of new anticancer therapy, or Subject Study Completion or Termination occurs. |
| Cryoablation | PROCEDURE | Cryoablation procedure (single session) of one tumor mass between Cycles 3 and 4 of nirogacestat treatment |
Double-Blind Key Inclusion Criteria: * Participant has histologically confirmed DT/AF (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 naïve, measurably progressi...