Abstract OT-03-06: Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer (NeoSTAR)
Authors: Spring Laura M. , Tolaney Sara M. , Desai Neelam , Comander Amy , Mulvey Therese , Krop Ian E. , Winer Eric P. , Mittendorf Elizabeth A. , Ellisen Leif W. , Bardia Aditya 
Published: February 2021

Abstract
Background: Optimizing treatments for triple negative breast cancer (TNBC) in the localized breast cancer setting is key to preventing metastatic recurrences and reducing mortality from this devastating disease. Sacituzumab Govitecan (SG), a novel antibody-drug conjugate in which the topoisomerase 1 inhibitor SN-38 (the active metabolite of irinotecan) is coupled to a humanized monoclonal antibody targeting the tumor antigen Trop-2, was granted FDA accelerated approval in April 2020 for treatment of patients with metastatic TNBC. The NeoSTAR clinical trial is evaluating SG in the neoadjuvant setting for patients with localized TNBC. Trial design: This is a single arm phase II study of neoadjuvant SG in patients with localized TNBC. SG will be administered via an IV infusion on Days 1, 8 of each 21-day cycle at a starting dose of 10 mg/kg for 4 cycles. After 4 cycles, patients who have biopsy-proven residual disease will have the option to receive additional standard neoadjuvant therapy at the discretion of the treating physician and subsequently proceed to surgery. Those with a complete response on imaging may proceed directly to surgery. A baseline research biopsy prior to initiation of study therapy is required as well as tissue collection following treatment with SG (either at surgery or via biopsy prior to additional neoadjuvant therapy). Eligibility criteria: Patients ≥ 18 years of age with previously untreated primary TNBC as determined by the local institution according to ASCO/CAP criteria will be enrolled. Patients must either have a primary tumor &gt;1 cm measured by imaging (cT1c-T4), or be node positive. An ECOG performance score of 0 or 1, and adequate bone marrow, hepatic, and renal function is required. Specific aims: The primary objective is to assess the pathological complete response (pCR) rate in breast and lymph nodes (ypT0/isN0) with SG. Secondary objectives include assessment of radiological response rate, evaluation of the safety and tolerability of SG (CTCAE v5.0), disease-free survival (DFS), and quality of life (EORTC QLQ-C30). Exploratory objectives include assessment of potential predictive biomarkers, including Trop-2 expression, DNA damage response markers and immunological markers, as well as changes in cell free DNA with SG. Statistical methods: The primary analysis is based on the estimated pCR rate with SG and will be provided as a proportion (with two-sided 95% confidence interval). Accounting for up to a 14% drop out rate, a sample size of 43 patients will provide 80% power to exclude a lower limit of pCR of 20% (alpha 0.05, two-sided test). DFS will be analyzed using Kaplan-Meier methods and descriptive statistics. Target Accrual: 50 patients. Contact: Dr. Laura Spring (LSpring@mgh.harvard.edu) Clinicaltrials.gov #: NCT04230109
Citation Format: Laura M. Spring, Sara M. Tolaney, Neelam Desai, Amy Comander, Therese Mulvey, Ian E. Krop, Eric P. Winer, Elizabeth A. Mittendorf, Leif W. Ellisen, Aditya Bardia. Phase 2 study of response-guided neoadjuvant sacituzumab govitecan (IMMU-132) in patients with localized triple-negative breast cancer (NeoSTAR) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-03-06.