Ogsiveo (nirogacestat) / SpringWorks Therap 
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 40 Diseases   16 Trials   16 Trials   530 News 


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  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap
    Journal:  Timed Notch Inhibition Drives Photoreceptor Fate Specification in Human Retinal Organoids. (Pubmed Central) -  Sep 29, 2022   
    Hence, the goal of our current study was to accelerate and synchronize photoreceptor differentiation in retinal organoids by inhibiting the Notch signaling pathway at different developmental time-points using a small molecule, PF-03084014 (PF)...Bulk RNA sequencing analysis mirrored the immunohistochemistry data and quantitative PCR confirmed Notch effector inhibition. Timing the Notch pathway inhibition in human retinal organoids to align with progenitor competency stages can yield an enriched population of early cone or rod photoreceptors.
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap, AL102 / Ayala Pharma, Novartis
    Review, Journal:  Molecular pathogenesis of desmoid tumor and the role of γ-secretase inhibition. (Pubmed Central) -  Sep 8, 2022   
    Two GSIs, nirogacestat (PF-03084014) and AL102 are in later-stage clinical development; nirogacestat is being evaluated in a phase 3, randomized, placebo-controlled trial while AL102 is being evaluated in a phase 2/3, dose-finding (part A) and placebo-controlled (part B) trial. This review summarizes current understanding of the molecular pathogenesis of DT focusing on dysregulation of the Wnt signaling pathway, crosstalk with the Notch pathway, and the potential therapeutic role for GSIs in DT.
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap, Cotellic (cobimetinib) / Exelixis, Roche, Zelboraf (vemurafenib) / Roche
    Journal:  BRAF Metastatic Melanoma Patient-derived Organoids and Docking Analysis to Predict the Response to Targeted Therapy. (Pubmed Central) -  Aug 11, 2022   
    Tumor analysis showed that BRAF displayed both increased phosphorylation of Erk1/2 at cytoplasmic level and activation of Notch resistance signaling. This prompted us to inhibit Notch signaling with Nirogacestat, achieving a greater antitumor response and providing PDOs-based evaluation of treatment efficacy in such rare metastatic melanoma.
  • ||||||||||  Ogsiveo (nirogacestat) / SpringWorks Therap
    Trial completion date, Trial primary completion date:  Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (clinicaltrials.gov) -  Jul 21, 2022   
    P3,  N=142, Active, not recruiting, 
    b + indicates improvement. Trial completion date: Mar 2023 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Apr 2022
  • ||||||||||  Ogsiveo (nirogacestat) / SpringWorks Therap
    Enrollment open, Trial initiation date:  Nirogacestat in Ovarian Granulosa Cell Tumors (clinicaltrials.gov) -  Jul 15, 2022   
    P2,  N=43, Recruiting, 
    Trial completion date: Mar 2023 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Apr 2022 Not yet recruiting --> Recruiting | Initiation date: May 2022 --> Aug 2022
  • ||||||||||  Ogsiveo (nirogacestat) / SpringWorks Therap
    Trial completion date, Trial primary completion date, Surgery:  A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery (clinicaltrials.gov) -  Jun 2, 2022   
    P2,  N=35, Recruiting, 
    Trial completion date: Oct 2028 --> Oct 2029 | Initiation date: Apr 2022 --> Oct 2022 | Trial primary completion date: Oct 2028 --> Oct 2029 Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: Dec 2024 --> Mar 2025
  • ||||||||||  Review, Journal:  Current management and recent progress in desmoid tumors. (Pubmed Central) -  May 18, 2022   
    P3
    In addition to nirogacestat, the gamma-secretase inhibitor AL102 is being investigated for the treatment of patients with progressing desmoid tumors in the phase II/III RINGSIDE trial. Finally, the beta-catenin inhibitor Tegavivint (BC2059) is being investigated in a phase 1 open-label trial in patients with a proven primary or recurrent desmoid tumor that is unresectable and symptomatic or progressive.
  • ||||||||||  foscenvivint (PRI724) / PRISM Pharma, Ohara Pharma, nirogacestat (PF-03084014) / SpringWorks Therap, Daurismo (glasdegib) / Pfizer
    FORCING LEUKAEMIC STEM CELL TO LEAVE QUIESCENT STATE BY INHIBITING HEDGEHOG, NOTCH AND WNT/BETA-CATENIN SIGNALLING PATHWAYS () -  May 13, 2022 - Abstract #EHA2022EHA_735;    
    They were treated during 24-48 hours with Glasdegib, Nirogacestat and PRI-724 which target Smoothened (Hedgehog), Gamma-Secretase (Notch) and Beta-Catenin (Wnt) proteins respectively...Cytarabine was employed during 48-72 hours in cell lines or during 24-48 hours in primary samples...Nevertheless, inhibition of Hh, Notch and WNT pathways reduce the quiescent population either measuring the disease as a whole or looking at the LSC population. Differences observed between different AML cell lines regarding increase of the citotoxicity might be explained by AML genetic heterogeneity.
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap, Nexavar (sorafenib) / Bayer, Amgen
    Cryoablation as an effective treatment for desmoid tumors: A single-institution case series. () -  Apr 28, 2022 - Abstract #ASCO2022ASCO_3188;    
    Our data support cryoablation as an effective therapy for decreasing tumor burden in multi-treatment resistant desmoid tumor patients. Although larger studies are needed to assess efficacy and safety, with an ORR of over 70% and a disease control rate of over 75%, cryoablation demonstrates promising results without the toxicity of systemic therapy and thus may be an effective strategy for multi-treatment resistant desmoid tumors.
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap
    Extended progression-free survival and long-term safety of nirogacestat in patients with desmoid tumors. (Available On Demand; 449) -  Apr 28, 2022 - Abstract #ASCO2022ASCO_3117;    
    P2, P3
    No patients receiving nirogacestat have progressed after a median of more than 4 years of treatment. The long duration of responses and lack of tumor progressions observed in this trial has informed the design of a phase III trial in pts with progressing desmoid tumors (NCT03785964) that is currently underway.
  • ||||||||||  Ogsiveo (nirogacestat) / SpringWorks Therap
    New P2 trial:  Nirogacestat in Ovarian Granulosa Cell Tumors (clinicaltrials.gov) -  Apr 26, 2022   
    P2,  N=43, Not yet recruiting, 
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap
    Journal:  Paracrine production of IL-6 promotes a hypercoagulable state in pancreatic cancer. (Pubmed Central) -  Jan 13, 2022   
    Finally, the animal study showed that knockdown of Jagged-1/2 or blockade of the Jagged/Notch pathway by Nirogacestat could alleviate pancreatic cancer-induced hypercoagulability. Accordingly, our findings clarified the key role of the Jagged/Notch/IL-6/STAT3 feedback loop in the development of a hypercoagulable state in pancreatic cancer, which also provides new therapeutic strategies for pancreatic cancer patients who suffer from hypercoagulability.
  • ||||||||||  nirogacestat (PF-03084014) / SpringWorks Therap, Blenrep (belantamab mafodotin) / GSK
    Journal, Combination therapy:  Belantamab mafodotin in combination with novel agents in relapsed/refractory multiple myeloma: DREAMM-5 study design. (Pubmed Central) -  Dec 16, 2021   
    P1/2
    Here, we describe the rationale and design of DREAMM-5, an ongoing Phase I/II platform study evaluating the safety and efficacy of belamaf combined with novel agents, including GSK3174998 (OX40 agonist), feladilimab (an ICOS; GSK3359609), nirogacestat (a gamma-secretase inhibitor; PF-03084014) and dostarlimab (a PD-1 blocker) versus belamaf monotherapy for patients with relapsed/refractory multiple myeloma. Clinical trial registration: NCT04126200 (ClinicalTrials.gov).