SpringWorks Therapeutics Announces Dosing of First Patient in Phase 1b Combination Study Evaluating Nirogacestat and Janssen’s BCMA Bispecific Antibody Teclistamab in Patients with Relapsed or Refractory Multiple Myeloma
- Category: Small Molecules
- Published on Friday, 02 April 2021 11:47
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STAMFORD, CT, USA I April 01, 2021 I SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a clinical-stage biopharmaceutical company focused on developing life-changing medicines for patients with severe rare diseases and cancer, today announced that the first patient has been dosed in a Phase 1b clinical trial evaluating nirogacestat, an investigational gamma secretase inhibitor (GSI) being developed by SpringWorks, in combination with teclistamab, an investigational bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3 being developed by Janssen Research & Development, LLC (Janssen), in patients with relapsed or refractory multiple myeloma.
Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells. In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, which may enhance the activity of BCMA-targeted therapies.
“We are very pleased that patients have been dosed in this study, which represents the first clinical study combining nirogacestat with a bispecific antibody in patients with multiple myeloma,” said Saqib Islam, Chief Executive Officer of SpringWorks Therapeutics. “We are advancing nirogacestat as a cornerstone of BCMA combination therapy across modalities and look forward to the enrollment of patients into multiple Phase 1 studies and generating data with our BCMA collaborators in 2021.”
The Phase 1b trial (NCT04722146), which is part of a multi-arm trial being conducted by Janssen, is an open-label study to evaluate the safety, tolerability and preliminary efficacy of nirogacestat in combination with teclistamab in patients with relapsed or refractory multiple myeloma. The trial is being advanced pursuant to a clinical collaboration and supply agreement that SpringWorks entered into with Janssen Biotech, Inc. in September 2020. Under the terms of the agreement, Janssen is assuming all costs associated with the Phase 1b study, other than expenses related to the supply of nirogacestat. SpringWorks has formed a joint oversight committee with Janssen to coordinate the sharing of study results, regulatory and other activities in connection with the study.
In addition to its ongoing clinical collaborations with BCMA-directed therapies, SpringWorks is conducting a global Phase 3, double-blind, randomized, placebo-controlled clinical trial (the DeFi Trial) to evaluate nirogacestat as a monotherapy in adults with progressing desmoid tumors.
Nirogacestat is an investigational, oral, selective, small molecule gamma secretase inhibitor in Phase 3 clinical development for desmoid tumors, which are rare and often debilitating and disfiguring soft-tissue tumors. Gamma secretase cleaves multiple transmembrane protein complexes, including Notch, which is believed to play a role in activating pathways that contribute to desmoid tumor growth.
In addition, gamma secretase has been shown to directly cleave membrane-bound BCMA, resulting in the release of the BCMA extracellular domain, or ECD, from the cell surface. By inhibiting gamma secretase, membrane-bound BCMA can be preserved, increasing target density while reducing levels of soluble BCMA ECD, which may serve as decoy receptors for BCMA-directed therapies. Nirogacestat’s ability to enhance the activity of BCMA-directed therapies has been observed in preclinical models of multiple myeloma. SpringWorks is evaluating nirogacestat as a BCMA potentiator and has five collaborations with industry-leading BCMA developers to evaluate nirogacestat in combinations across modalities, including with an antibody-drug conjugate, two CAR T cell therapies and two bispecific antibodies. In addition, SpringWorks and Fred Hutchinson Cancer Research Center have entered into a sponsored research agreement to further characterize the ability of nirogacestat to modulate BCMA and potentiate BCMA directed therapies using a variety of preclinical and patient-derived multiple myeloma models developed by researchers at Fred Hutch.
Nirogacestat has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors and from the European Commission for the treatment of soft tissue sarcoma. The FDA also granted Fast Track and Breakthrough Therapy Designations for the treatment of adult patients with progressive, unresectable, recurrent or refractory desmoid tumors or deep fibromatosis.
About SpringWorks Therapeutics
SpringWorks is a clinical-stage biopharmaceutical company applying a precision medicine approach to acquiring, developing and commercializing life-changing medicines for underserved patient populations suffering from devastating rare diseases and cancer. SpringWorks has a differentiated portfolio of small molecule targeted oncology product candidates and is advancing two potentially registrational clinical trials in rare tumor types, as well as several other programs addressing highly prevalent, genetically defined cancers. SpringWorks’ strategic approach and operational excellence in clinical development have enabled it to rapidly advance its two lead product candidates into late-stage clinical trials while simultaneously entering into multiple shared-value partnerships with industry leaders to expand its portfolio. For more information, please visit www.springworkstx.com, and follow @SpringWorksTx on Twitter and LinkedIn.
SOURCE: SpringWorks Therapeutics