Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Nirogacestat oral tablet
Nirogacestat · 7 trials · 7 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
Area under the concentration-time curve from dosing extrapolated to infinity. AUCinf = (AUClast + Clast/Kel) where Clast is the plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis and Kel is the terminal elimination phase rate constant estimated by linear regression based on observations justified to describe the terminal phase on the log-linear concentration-time profile.
Maximum observed plasma concentration. Observed directly from the data.
Serum AUCinf of nirogacestat.
Serum Cmax of nirogacestat.
Serum AUCinf of nirogacestat.
Serum Cmax of nirogacestat.
| 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 |
| Nirogacestat and CYP cocktail | EXPERIMENTAL | Nirogacestat 100 mg BID will be administered orally from Day 1 through Day 17 and an oral dose of CYP cocktail (CYP2B6 \[bupropion 20 mg\], CYP2C8 \[repaglinide 0.05 mg\], CYP2C9 \[flurbiprofen 10 mg\], CYP2C19 \[omeprazole 10 mg\], and CYP3A4 \[midazolam 1 mg\]) will be administered on Day -3, and again on Day 15. |
| Period 1 - Nirogacestat Dose (Reference) | ACTIVE_COMPARATOR | Nirogacestat will be administered, after at least a 10-hour fast, in the morning on Day 1, Day 6, and Day 17 |
| Period 2 - Nirogacestat and Famotidine (Test) | ACTIVE_COMPARATOR | Famotidine will be administered as an oral tablet 2 hours after the administration of nirogacestat on Day 6. |
| Period 3 Nirogacestat and Rabeprazole (Test) | ACTIVE_COMPARATOR | Rabeprazole will be administered as an oral tablet in the evenings on Day 10 through Day 16. |
| 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 |
| Nirogacestat and Cocktail of CYP Specific Probe Substrates | DRUG | Drug: Nirogacestat 100 mg tablet Day 1 through Day 17 and Drug: Cocktail of CYP Specific Probe Substrates administered Day 15. |
| Nirogacestat and Famotidine | DRUG | oral dose of 150 mg nirogacestat \& oral dose of 40 mg famotidine |
| Nirogacestat and Rabeprazole | DRUG | oral dose of 150 mg nirogacestat and oral dose of 20 mg rabeprazole |
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 developed for desmoid tumors, also known as aggressive fibromatosis. It is also being studied in ovarian granulosa-stromal tumors and in healthy volunteers. The drug is currently in Phase 3 clinical development for desmoid tumors.
Nirogacestat is a gamma-secretase inhibitor that targets multiple components of the gamma-secretase complex, including APH1A, PSENEN, APH1B, PSEN1, NCSTN, and PSEN2. By inhibiting this enzyme complex, the drug aims to block Notch signaling, which is implicated in desmoid tumor growth.
Nirogacestat is being developed by SpringWorks Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker symbol SWTX. The company is conducting clinical trials of the drug in desmoid tumors and other conditions.
Nirogacestat is in Phase 3 clinical development for desmoid tumors. It has received several FDA designations, including Priority Review, Fast Track, Orphan Drug, and Breakthrough Therapy. The drug is investigational and has not been approved by the FDA.
Nirogacestat has been studied in several clinical trials. NCT03785964 is a completed Phase 3 trial in desmoid tumors with 142 participants. NCT05879146 is a recruiting Phase 2 trial in tumors, NCT05949099 is a recruiting Phase 2 trial combining cryoablation, and NCT07170644 is an active Phase 2 trial in Japanese adults with desmoid tumors.
Yes, Nirogacestat oral tablet is the formulation of the drug being developed by SpringWorks Therapeutics. The oral tablet is the form used in clinical trials for desmoid tumors and other conditions. The drug is also known by its chemical name, nirogacestat.