Federman N. Molecular pathogenesis of desmoid tumor and the role of γ-secretase inhibition. NPJ Precis Oncol. 2022;6(1):62.

Article  PubMed  PubMed Central  Google Scholar 

Shearer T, Williams RL, Johnson M, et al. Population pharmacokinetic-pharmacodynamic model of nirogacestat effects on B-cell maturation antigen in healthy subjects [abstract no. 8027 plus poster]. J Clin Oncol. 2023;41(16 Suppl):8027.

Article  Google Scholar 

Zheng C, Huang J, Xu G, et al. The Notch signaling pathway in desmoid tumor: recent advances and the therapeutic prospects. Biochim Biophys Acta Mol Basis Dis. 2024;1870(1): 166907.

Article  PubMed  Google Scholar 

Kummar S, O’Sullivan Coyne G, Do KT, et al. Clinical activity of the γ-secretase inhibitor PF-03084014 in adults with desmoid tumors (aggressive fibromatosis). J Clin Oncol. 2017;35(14):1561–9.

Article  PubMed  PubMed Central  Google Scholar 

Li X, Tian B, Liu M, et al. Adult-type granulosa cell tumor of the ovary. Am J Cancer Res. 2022;12(8):3495–511.

PubMed  PubMed Central  Google Scholar 

Konstantinopoulos P, Lewis J, Shearer T, et al. Trial in progress: a phase two trial of nirogacestat, a gammasecretase inhibitor, in patients with recurrent ovarian granulosa cell tumors (NCT05348356) [abstract no. 1284]. Gynecol Oncol. 2023;176:S177–8.

Article  Google Scholar 

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces FDA approval of OGSIVEO™ (nirogacestat) as the first and only treatment for adults with desmoid tumors [media release]. 27 Nov 2023. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. Nirogacestat: US prescribing information. 2023. https://www.ogsiveo.com/. Accessed 29 Nov 2023.

Leypoldt L, Callander N, Richardson P, et al. Low-dose belantamab mafodotin (belamaf) in combination with nirogacestat vs belamaf monotherapy in patients with relapsed/refractory multiple myeloma (RRMM): phase I/II DREAMM-5 platform sub-study 3: P330. Oncol Res Treat. 2023;46:176–7.

Google Scholar 

US Food & Drug Administration. FDA approves first therapy for rare type of non-cancerous tumors [media release]. 27 Nov 2023. https://www.fda.gov/.

SpringWorks Therapeutics Inc. Corporate presentation (December 2023) 2023. https://ir.springworkstx.com/. Accessed 15 Dec 2023.

Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med. 2023;388(10):898–912.

Article  PubMed  Google Scholar 

Allogene Therapeutics, SpringWorks Therapeutics Inc. Allogene Therapeutics and SpringWorks Therapeutics announce clinical collaboration to evaluate ALLO-715 in combination with nirogacestat in multiple myeloma [media release]. 13 Jan 2020. https://www.allogene.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces clinical collaboration with Janssen to evaluate nirogacestat in combination with teclistamab in patients with relapsed or refractory multiple myeloma [media release]. 14 Sep 2020. https://ir.springworkstx.com/.

Precision Biosciences, SpringWorks Therapeutics Inc. Precision BioSciences and SpringWorks Therapeutics announce clinical collaboration to evaluate PBCAR269A in combination with nirogacestat in patients with relapsed or refractory multiple myeloma [media release]. 21 Sep 2020. https://precisionbiosciences.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces clinical collaboration with Pfizer Inc. to evaluate nirogacestat in combination with PF06863135 in patients with relapsed or refractory multiple myeloma [media release]. 5 Oct 2020. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces clinical collaboration with Seagen to evaluate nirogacestat in combination with SEA-BCMA in patients with relapsed or refractory multiple myeloma [media release]. 7 Jun 2021. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces clinical collaboration with AbbVie to evaluate nirogacestat in combination with ABBV-383 in patients with relapsed or refractory multiple myeloma [media release]. 10 Aug 2021. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces clinical trial collaboration and supply agreement with Regeneron to evaluate nirogacestat in combination with REGN5458 in patients with relapsed or refractory multiple myeloma [media release]. 19 Apr 2022. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks announces expansion of global, non-exclusive collaboration with GSK for nirogacestat in combination with blenrep in patients with multiple myeloma [media release]. 7 Sep 2022. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces global clinical collaboration with GlaxoSmithKline to evaluate nirogacestat in combination with belantamab mafodotin in patients with relapsed or refractory multiple myeloma [media release]. 27 Jun 2019. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics enters into sponsored research agreement with Fred Hutchinson Cancer Research Center to further evaluate nirogacestat as a BCMA potentiator in multiple myeloma [media release]. 18 Sep 2020. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics enters into research collaboration with leading cancer institute to further evaluate nirogacestat as a BCMA potentiator in multiple myeloma [media release]. 30 Aug 2021. https://ir.springworkstx.com/.

SpringWorks Therapeutics Inc. SpringWorks Therapeutics announces collaboration with Children’s Oncology Group to conduct a phase 2 clinical trial of nirogacestat in pediatric patients with desmoid tumors and reports publication of nirogacestat case series in pediatric/young adult desmoid tumor patients [media release]. 16 Sep 2020. https://ir.springworkstx.com/.

Wei P, Walls M, Qiu M, et al. Evaluation of selective gamma-secretase inhibitor PF-03084014 for its antitumor efficacy and gastrointestinal safety to guide optimal clinical trial design. Mol Cancer Ther. 2010;9(6):1618–28.

Article  PubMed  Google Scholar 

Shang H, Braggio D, Lee YJ, et al. Targeting the Notch pathway: a potential therapeutic approach for desmoid tumors. Cancer. 2015;121(22):4088–96.

Article  PubMed  Google Scholar 

Chen X, Chen X, Zhou Z, et al. Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-induced bone resorption in vivo. Exp Cell Res. 2019;382(1): 111470.

Article  MathSciNet  PubMed  Google Scholar 

Williams R, Shearer T, Lohmer L. A concentration-QT analysis identifes no meaningful effect of nirogacestat or itraconazole on QTcF interval. Clin Pharmacol Drug Dev. 2023;12(Suppl 1):120–1.

Google Scholar 

O’Sullivan Coyne GH, Kummar S, Steinberg SM, et al. Extended progression-free survival and long-term safety of nirogacestat in patients with desmoid tumors [abstract no. 11545]. J Clin Oncol. 2022;40(16 Suppl):11545.

Article  Google Scholar 

Callander N, Richardson P, Hus M, et al. Low-dose belantamab mafodotin (BELAMAF) in combination with nirogacestat vs belamaf monotherapy in patients with relapsed/refractory multiple myeloma (RRMM): phase 1/2 DREAMM-5 platform sub-study 3 [abstract no. P913]. HemaSphere. 2023;7(S3): e9722122.

Article  PubMed Central  Google Scholar 

Offner F, Decaux O, Hulin C, et al. Teclistamab (TEC) + nirogacestat (NIRO) in relapsed/refractory multiple myeloma (RRMM): the phase 1b MajesTEC-2 study. HemaSphere. 2023;7(S3): e1257964.

Article  PubMed Central  Google Scholar