Aditya Bardia, Sheng Sun, Nayana Thimmiah, James T Coates, Bogang Wu, Rachel O Abelman, Laura Spring, Beverly Moy, Phoebe Ryan, Mark N Melkonyan, Ann Partridge, Dejan Juric, Jeffrey Peppercorn, Heather Parsons, Seth A Wander, Victoria Attaya, Brenda Lormil, Maria Shellock, Aiko Nagayama, Veerle Bossuyt, Steven J Isakoff, Sara M Tolaney, Leif W Ellisen
PURPOSE: The Antibody-Drug Conjugate (ADC) Sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly (ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1 inhibitors and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess proof-of-mechanism and clinical feasibility for SG and talazoparib employing an innovative sequential dosing schedule...
May 6, 2024: Clinical Cancer Research