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Therapy Name | Nirogacestat |
Synonyms | |
Therapy Description |
Ogsiveo (nirogacestat) is a small molecule that selectively binds to Gamma-secretase and inhibits its proteolytic activity on downstream targets including NOTCH receptor proteins, thus blocking NOTCH pathway activation in cancer (PMID: 28887726, PMID: 31211955). Ogsiveo (nirogacestat) is FDA-approved for use in patients with progressing desmoid tumors (FDA.gov). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Nirogacestat | Ogsiveo | PF-03084014|PF 03084014|PF03084014 | Gamma secretase inhibitor 13 | Ogsiveo (nirogacestat) is a small molecule that selectively binds to Gamma-secretase and inhibits its proteolytic activity on downstream targets including NOTCH receptor proteins, thus blocking NOTCH pathway activation in cancer (PMID: 28887726, PMID: 31211955). Ogsiveo (nirogacestat) is FDA-approved for use in patients with progressing desmoid tumors (FDA.gov). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
APC inact mut | desmoid tumor | predicted - sensitive | Nirogacestat | Case Reports/Case Series | Actionable | In a clinical case study, Ogsiveo (nirogacestat) resulted in stable disease lasting 9 months in a patient with a patient with a desmoid tumor harboring an inactivating APC mutation (PMID: 32762028). | 32762028 |
APC mutant | desmoid tumor | predicted - sensitive | Nirogacestat | Phase III | Actionable | In a Phase III trial (DeFi), Ogsiveo (nirogacestat) treatment resulted in improved progression-free survival (HR=0.21, p=0.016) and improved objective response rate (38% (5/13) vs. 13% (2/16)) compared to treatment with placebo in patients with desmoid tumors harboring mutations in APC (J Clin Oncol 42, 2024 (suppl 16; abstr 11558); NCT03785964). | detail... |
APC R1450* APC LOH | desmoid tumor | predicted - sensitive | Nirogacestat | Case Reports/Case Series | Actionable | In a clinical case study, Ogsiveo (nirogacestat) resulted in tumor regression in a pediatric patient with a desmoid tumor harboring APC R1450* and loss of the APC heterozygosity who stayed on treatment for 6 months (PMID: 32762028). | 32762028 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
NCT04195399 | Phase II | Nirogacestat | A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery | Active, not recruiting | USA | NZL | CAN | AUS | 1 |
NCT02137564 | Phase II | Nirogacestat | Gamma Secretase Inhibitor PF-03084014 in Treating Patients With AIDS-Associated Kaposi Sarcoma | Withdrawn | 0 | |
NCT01981551 | Phase II | Nirogacestat | Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis | Completed | USA | 0 |
NCT03785964 | Phase III | Nirogacestat | Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (DeFi) | Active, not recruiting | USA | NLD | ITA | GBR | DEU | CAN | BEL | 0 |
NCT02955446 | Expanded access | Nirogacestat | Compassionate Use Protocol for PF-03084014 in Patients With Advanced Solid Tumor Malignancies | No longer available | USA | 0 |
NCT02109445 | Phase II | Gemcitabine + Nab-paclitaxel Nirogacestat | Study Of PF-03084014 In Combination With Gemcitabine And Nab-Paclitaxel In Patients With Metastatic Pancreatic Adenocarcinoma Not Previously Treated With Anticancer Therapies | Terminated | USA | 0 |
NCT05949099 | Phase II | Nirogacestat | Study of Cryoablation and Nirogacestat for Desmoid Tumor | Recruiting | USA | 0 |
NCT05879146 | Phase II | Nirogacestat | Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study | Not yet recruiting | USA | 0 |
NCT05348356 | Phase II | Nirogacestat | Nirogacestat in Ovarian Granulosa Cell Tumors | Active, not recruiting | USA | POL | CAN | 0 |
NCT02299635 | Phase II | Nirogacestat | A Study Evaluating PF-03084014 In Patients With Advanced Breast Cancer With Or Without Notch Alterations | Terminated | USA | POL | ITA | HUN | GBR | ESP | 0 |