Antibody-Drug Conjugate Sacituzumab Govitecan Enables a Sequential TOP1/PARP Inhibitor Therapy Strategy in Patients with Breast Cancer.

ABSTRACT:

Purpose

The antibody-drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP and TOP1 inhibitors failed due to dose-limiting myelosuppression. Here, we assess the proof-of-mechanism and clinical feasibility for SG and talazoparib (TZP) employing an innovative sequential dosing schedule.

Patients and methods

In vitro models tested pharmacodynamic endpoints, and in a phase 1b clinical trial (NCT04039230), 30 patients with metastatic triple-negative breast cancer (mTNBC) received SG and TZP in a concurrent (N = 7) or

SUBMITTER: Bardia A 

PROVIDER: S-EPMC11247314 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature