A Phase I Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients with Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors
FHD-609 showed dose-dependent increases in systemic FHD-609 exposure and pharmacodynamic response profiles. The maximum tolerated doses were identified (40 mg twice weekly/80 mg once weekly) and preliminary clinical activity was observed. Future studies of BRD9 degraders will require strict cardiac monitoring given the QTc prolongation observed in this study.
Authors
- Kim Horrigan
- Meredith McKean (ORCID: https://orcid.org/0000-0003-0944-7418)
- Andrew J. Wagner (ORCID: https://orcid.org/0000-0002-4384-9448)
- Jonathan C. Trent (ORCID: https://orcid.org/0000-0001-6169-5238)
- Michael P. Collins (ORCID: https://orcid.org/0000-0002-1806-6775)
- Claudia Valverde (ORCID: https://orcid.org/0000-0003-4107-8616)
- Jessica Piel
- Michael J. Wagner (ORCID: https://orcid.org/0000-0002-8812-1653)
- Ariel Lefkovith (ORCID: https://orcid.org/0000-0003-4519-0429)
- Mark Agulnik (ORCID: https://orcid.org/0000-0003-3513-3519)
- Mrinal M. Gounder (ORCID: https://orcid.org/0000-0001-8468-0119)
- Jean‐Yves Blay (ORCID: https://orcid.org/0000-0001-7190-120X)
- Alexander J. Lazar (ORCID: https://orcid.org/0000-0002-6395-4499)
- Silvia Stacchiotti (ORCID: https://orcid.org/0000-0002-1742-8666)
- Scott Innis
- J. Andrew Livingston (ORCID: https://orcid.org/0000-0002-1337-3282)
- Alex Ballesteros‐Perez
- Axel Le Cesne (ORCID: https://orcid.org/0000-0002-8006-8659)
- Gregory M. Coté (ORCID: https://orcid.org/0000-0003-0181-886X)
- Alfonso Quintás‐Cardama (ORCID: https://orcid.org/0000-0002-4623-8917)
- Samuel Agresta
- Alexis Khalil (ORCID: https://orcid.org/0009-0008-9231-7641)
- Denice Hickman
- Tina Zhao
- Kathleen Healy
- Sarah A. Reilly
Institutions
- Hebron University (PS)
- City Of Hope National Medical Center (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- University of Miami (US)
- Cornell University (US)
- Institut Gustave Roussy (FR)
- Kettering University (US)
- Massachusetts General Hospital (US)
- Fred Hutch Cancer Center (US)
- Agios Pharmaceuticals (United States) (US)
- Sarah Cannon (US)
- Centre Léon Bérard (FR)
- City of Hope (US)
- Dana-Farber Cancer Institute (US)
- Certara (United States) (US)
- Vall d'Hebron Hospital Universitari (ES)
- Tennessee Oncology (US)
- Tumori Foundation (US)
- Center for Cancer Research (US)
- Io Therapeutics (United States) (US)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Sylvester Comprehensive Cancer Center (US)
- International Drug Development (FR)
- Foghorn Therapeutics (United States) (US)
Publication Details
- Journal
- Clinical Cancer Research
- Published
- 2024-12-11
- DOI
- https://doi.org/10.1158/1078-0432.ccr-24-2583
- Citations
- 29
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 6.78