Synonyms: Ogsiveo® | PF-03084014 | PF3084014 | Z-3181
nirogacestat is an approved drug (FDA (2023))
Compound class:
Synthetic organic
Comment: Nirogacestat (PF-3084014) is compound 14f in [2] where it is described as a centrally active γ-secretase inhibitor. It is a reversible, non-competitive, and orally bioactive agent. It was proposed an an anti-tumour agent [1,3,11-12].
PF-3084014 was also reported as an inhibitor of the NOTCH signalling pathway which bolstered its oncology credentials [8,11], since NOTCH inhibition promotes cell cycle arrest and induces apoptosis in tumour cells. |
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No information available. |
Summary of Clinical Use ![]() |
This compound was assessed in clinical trials for the treatment of several types of cancer. Click here to view the full list of PF-03084014 trials registered with ClinicalTrials.gov. A number of PF-03084014 clinical trials appear to have been stopped or withdrawn, apparently for business reasons. Notes against these trials state that there were no safety/efficacy concerns behind the decisions. Development for desmoid tumours [9] (a rare and aggressive soft tissue sarcoma) was continued by SpringWorks Therapeutics. There were no FDA-approved treatments for desmoid tumours at the time. Based on efficacy data coming from clinical trials [10], nirogacestat was granted FDA orphan designation for this indication in mid-2018. EMA orphan drug designation followed in late 2019. In 2023, the FDA accepted nirogacestat for priority review as a treatment option for locally invasive, soft tissue desmoid tumours, and this culminated in full approval in November of that year [6-7]. Nirogacestat (Ogsiveo) was the first γ-secretase inhibitor to reach the clinic and was the first approved treatment for desmoid tumours. |
Clinical Trials | |||||
Clinical Trial ID | Title | Type | Source | Comment | References |
NCT04195399 | A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery | Phase 2 Interventional | Children's Oncology Group | ||
NCT01981551 | Phase II Trial of the Gamma-Secretase Inhibitor PF-03084014 in Adults With Desmoid Tumors/Aggressive Fibromatosis | Phase 2 Interventional | National Institutes of Health Clinical Center (CC) | ||
NCT03785964 | Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) | Phase 3 Interventional | SpringWorks Therapeutics, Inc. | 4-5 | |
NCT05348356 | Nirogacestat in Ovarian Granulosa Cell Tumors | Phase 2 Interventional | SpringWorks Therapeutics, Inc. |