Abstract OT1-07-05: TROPiCS-02: phase 3 study of Sacituzumab Govitecan (IMMU-132) in relapsed/refractory hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC)
Authors: Rugo Hope S , Bardia Aditya , Tolaney Sara M. , Arteaga Carlos , Cortes Javier , Sohn Joohyuk , Marmé Frederik , Hong Quan , Hofsess Scott , Olivo Martin , Fabrice André , Schmid Peter 
Published: March 2020

Abstract
Background: Patients (pts) with HR+/HER2- MBC for whom first- and second-line treatments have failed need additional treatment approaches. Trophoblast cell surface antigen 2 (Trop-2) is highly expressed in breast cancer and linked to poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate comprising an anti-Trop-2 monoclonal antibody conjugated to SN-38 (active metabolite of irinotecan) in a high drug-to-antibody ratio of 7.6. It has a unique hydrolysable linker that allows release of SN-38 intracellularly and in the tumor microenvironment. In the HR+/HER2- MBC cohort in the IMMU 132-01 phase 1/2 basket study, SG showed a 31% objective response rate (ORR), median progression-free survival (PFS) of 6.8 mo, and a predictable and manageable safety profile with low discontinuation rates due to adverse events (Kalinsky 2018 SABCS).
Trial Design: Trop-2 Investigation in Cancer with Sacituzumab (TROPiCS-02; NCT03901339) is a randomized, open-label, phase 3 study in pts with HR+/HER2- MBC and ≥1 measurable target lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 after failure of ≥2, but ≤4 prior chemotherapy regimens. Pts are randomized 1:1 to receive SG (10 mg/kg intravenously, days 1 and 8 every 21 days) or treatment of physician’s choice (TPC, determined pre-randomization: eribulin, capecitabine, gemcitabine, vinorelbine). Pts continue treatment until progression requiring discontinuation or unacceptable toxicity. Eligible pts are females or males ≥18 y old with documented evidence of HR+/HER2- MBC, Eastern Cooperative Oncology Group score of 0 or 1, and adequate safety laboratories. Pts must have received prior taxanes in any setting, ≥1 prior anticancer hormonal treatment, and ≥1 cyclin dependent kinase 4/6 inhibitor in the metastatic setting, with documented progression after most recent therapy. Pts also must be eligible to receive one of the TPC agents. The primary endpoints are PFS (local assessment) and ORR; additional endpoints include overall survival (OS), duration of response (DOR), and safety. The hazard ratio of the primary endpoint of PFS and its associated 95% confidence interval (CI) will be estimated using a Cox proportional-hazards model; the 2-sided 95% CIs of ORR will be calculated by the Clopper-Pearson exact method. Exploratory endpoints include Trop-2 expression and efficacy in relation to Trop-2 expression and blood and tumor biomarkers. Biomarker samples are taken at baseline, pre-dose at cycle 2, and at disease progression/end of treatment. Approximately 400 pts will be randomized across multiple countries.
Citation Format: Hope S Rugo, Aditya Bardia, Sara M. Tolaney, Carlos Arteaga, Javier Cortes, Joohyuk Sohn, Frederik Marmé, Quan Hong, Scott Hofsess, Martin Olivo, André Fabrice, Peter Schmid. TROPiCS-02: phase 3 study of Sacituzumab Govitecan (IMMU-132) in relapsed/refractory hormonal receptor-positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-07-05.