Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Nirogacestat Hydrobromide, Nirogacestat oral tablet, PF-03084014, Ogsiveo
Nirogacestat · 6 trials · 9 indications
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
The Kaplan-Meier method will be used to estimate the 2-year PFS defined as the time from study entry until disease progression or death from any cause.
Percentage of patients experiencing grade 3 or higher AEs will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. All grade 1 and 2 toxicities observed in \> 5% of participants and deemed related to study drug will be reported.
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
PK parameters of nirogacestat will be defined to quantify systemic exposure, drug clearance, terminal half-life and other pharmacokinetic characteristics. These PK parameters will be summarized with descriptive statistics, including means, medians, ranges, and standard deviations.
| 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. |
| Nirogacestat Open-Label | EXPERIMENTAL | Nirogacestat 150 mg by mouth, twice daily Nirogacestat oral tablet: Nirogacestat tablet |
| Treatment (nirogacestat) | EXPERIMENTAL | Patients receive nirogacestat PO BID on days 1-28. Cycles repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO and CT or MRI on study. Patients may also undergo x-ray imaging and blood sample collection on study. |
| Name | Type | Description |
|---|---|---|
| Nirogacestat oral tablet | DRUG | Nirogacestat tablet |
| Placebo Oral Tablet | DRUG | Sugar pill manufactured to mimic nirogacestat 50 mg tablet |
| Nirogacestat | DRUG | Given by PO |
| Cryoablation | PROCEDURE | Cryoablation procedure (single session) of one tumor mass between Cycles 3 and 4 of nirogacestat treatment |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Computed Tomography | PROCEDURE | Undergo CT |
| Echocardiography Test | PROCEDURE | Undergo ECHO |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Nirogacestat Hydrobromide | DRUG | Given PO |
| Quality-of-Life Assessment | OTHER | Ancillary studies |
| Questionnaire Administration | OTHER | Ancillary studies |
| X-Ray Imaging | PROCEDURE | Undergo x-ray |
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...
Nirogacestat is an investigational small molecule being studied for desmoid fibromatosis, also called desmoid tumor or aggressive fibromatosis, and for ovarian granulosa-stromal tumors. It is in Phase 2 clinical development and has received FDA designations including Priority Review, Fast Track, Orphan Drug, and Breakthrough Therapy.
Nirogacestat is an inhibitor of the gamma-secretase complex, targeting the presenilin and nicastrin components PSEN1, PSEN2, NCSTN, APH1A, APH1B, and PSENEN. By inhibiting this complex, it is designed to interfere with Notch pathway signaling, which is implicated in desmoid tumor growth.
Nirogacestat is being developed by SpringWorks Therapeutics, Inc., which trades under the ticker SWTX. The company is running Phase 2 studies of the oral tablet in desmoid tumors and ovarian granulosa cell tumors across the United States, Canada, Poland, and Japan.
Nirogacestat is in Phase 2 clinical development. It is investigational and has not been approved by the FDA. The program includes completed and ongoing Phase 2 trials, with one active trial, one completed trial, and additional studies recruiting or active but not recruiting.
Nirogacestat trials include NCT07170644 in Japanese adults with desmoid tumors, NCT05949099 studying cryoablation plus nirogacestat in desmoid tumor, NCT05879146 evaluating response and non-response in desmoid tumors, and NCT05348356 in ovarian granulosa cell tumors, which is completed.
Yes. Nirogacestat Hydrobromide and nirogacestat oral tablet are alternative names for nirogacestat, the small molecule developed by SpringWorks Therapeutics. Searches for any of these names refer to the same investigational Phase 2 drug candidate being studied in desmoid tumors and ovarian granulosa-stromal tumors.