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    DRUG:

    Ogsiveo (nirogacestat)

    i
    Other names: PF-03084014 , PF03084014, PF 03084014
    Company:
    EMD Serono
    Drug class:
    γ-secretase inhibitor
    Related drugs:
    10d
    Phase II clinical trial of nirogacestat in patients with relapsed ovarian granulosa cell tumours. (PubMed, Clin Transl Med)
    This Phase II clinical trial of a rare tumour achieved its enrolment target in under 1 year and completed primary analysis within 2 years. 87% (46 of 53 patients who received nirogacestat) had fresh or archival biopsies that were analysed by next-generation sequencing for mutational profiling. Of the 3 patients with activating NOTCH1 mutations, all achieved 6-month progression-free survival (PFS6); 8 other patients also achieved PFS6 but did not share a common mutation.
    P2 data • Journal
    |
    NOTCH1 (Notch 1) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • FOXL2 (Forkhead Box L2)
    |
    Ogsiveo (nirogacestat)
    1m
    NIR-OGT-201: Nirogacestat in Ovarian Granulosa Cell Tumors (clinicaltrials.gov)
    P2, N=53, Completed, SpringWorks Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2027 --> Jul 2025 | Trial primary completion date: Jul 2026 --> Jul 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    Ogsiveo (nirogacestat)
    2ms
    To Determine the Effect of CYP Induction Following Administration of Nirogacestat in Healthy Adult Male Participants (clinicaltrials.gov)
    P1, N=16, Recruiting, SpringWorks Therapeutics, Inc.
    New P1 trial
    |
    Ogsiveo (nirogacestat) • midazolam hydrochloride • omeprazole
    2ms
    A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, Children's Oncology Group | Trial completion date: Dec 2025 --> Mar 2026 | Trial primary completion date: Dec 2025 --> Mar 2026
    Trial completion date • Trial primary completion date
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    Ogsiveo (nirogacestat)
    2ms
    DREAMM 5: Platform Study of Belantamab Mafodotin as Monotherapy and in Combination With Anti-cancer Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov)
    P2, N=208, Active, not recruiting, GlaxoSmithKline | Trial completion date: Feb 2029 --> Mar 2027 | Trial primary completion date: Feb 2029 --> Apr 2025
    Trial completion date • Trial primary completion date
    |
    lenalidomide • Jemperli (dostarlimab-gxly) • dexamethasone • pomalidomide • Sarclisa (isatuximab-irfc) • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat) • feladilimab (GSK3359609) • GSK3174998
    3ms
    A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery (clinicaltrials.gov)
    P2, N=35, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2025 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    Ogsiveo (nirogacestat)
    3ms
    MajesTEC-2: A Study of Teclistamab With Other Anticancer Therapies in Participants With Multiple Myeloma (clinicaltrials.gov)
    P1, N=140, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2027 --> Oct 2027
    Trial completion date
    |
    lenalidomide • bortezomib • Darzalex (daratumumab) • pomalidomide • Ogsiveo (nirogacestat) • Tecvayli (teclistamab-cqyv)
    4ms
    Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (clinicaltrials.gov)
    P4, N=50, Recruiting, SpringWorks Therapeutics, Inc.
    New P4 trial
    |
    Ogsiveo (nirogacestat)
    4ms
    Evaluate the Effects of Famotidine or Rabeprazole on the PK of Nirogacestat (clinicaltrials.gov)
    P1, N=24, Recruiting, SpringWorks Therapeutics, Inc.
    New P1 trial
    |
    Ogsiveo (nirogacestat)
    4ms
    A Study of Nirogacestat in Japanese Adults With Desmoid Tumors/Aggressive Fibromatosis (DT/AF) (clinicaltrials.gov)
    P2, N=18, Recruiting, SpringWorks Therapeutics, Inc.
    New P2 trial
    |
    Ogsiveo (nirogacestat)
    5ms
    Repurposing nirogacestat, a gamma secretase enzyme inhibitor in desmoid tumors. (PubMed, Future Oncol)
    GS enzyme inhibitors such as semagacestat and avagacestat were explored in AD but the studies were paused because of adverse events attributed to their influence on the Notch pathway.Crosstalk between Notch and Wnt signaling pathways created a potential role for GS inhibitors in the treatment of malignancies such as glioblastoma multiforme, pancreatic, and breast cancers. Emphasis was placed on patient-reported outcomes (PRO) including the DT-specific tool, GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom Scale (GODDESS).Nirogacestat received Food and Drug Administration (FDA) approval in November 2023 for management of progressive, unresectable, recurrent, or refractory DT. Further studies are underway to investigate other GS inhibitors such as AL-102 in the management of DT.
    Review • Journal
    |
    APP (Amyloid Beta Precursor Protein)
    |
    Ogsiveo (nirogacestat) • varegacestat (AL102)
    5ms
    Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants With RRMM (clinicaltrials.gov)
    P1/2, N=14, Active, not recruiting, GlaxoSmithKline
    New P1/2 trial
    |
    dexamethasone • pomalidomide • Blenrep (belantamab mafodotin-blmf) • Ogsiveo (nirogacestat)