Abstract OT2-07-05: A phase III, randomized trial of sacituzumab govitecan (IMMU-132) vs treatment of physician choice (TPC) for metastatic triple-negative breast cancer (mTNBC)
Authors: Bardia A , Rugo HS , Horne H , Wegener WA , Goldenberg DM , O'Shaughnessy J 
Published: February 2018

Abstract
Background: Metastatic TNBC has an aggressive course with limited therapy options and poor survival. Sacituzumab govitecan (IMMU-132) is a novel antibody drug conjugate consisting of SN-38, the active metabolite of the topoisomerase I inhibitor, irinotecan, conjugated to a humanized mAb targeting Trop-2, which is highly expressed in most epithelial cancers, including TNBC. We previously reported that patients (pts) with mTNBC treated with IMMU-132 after a median of 5 prior therapies from initial diagnosis achieved a 30% objective response rate (ORR), 8.9 mo median duration of response (DOR), and an acceptable safety profile with nausea, neutropenia, and diarrhea the most common toxicities (Bardia et al., JCO, 2017). IMMU-132 was awarded Breakthrough Designation by the FDA based on this data. Accordingly, we are enrolling additional patients with relapsed/refractory mTNBC with intention of seeking regulatory approval as a ≥3rd-line therapeutic option.
Trial design: An international, open-label, Phase III study in pts with refractory/relapsed mTNBC after ≥2 prior chemotherapies for advanced disease or &gt;1 therapy for pts who progress within 12 months of adjuvant therapy (NCT02574455). Pts are randomized 1:1 to receive either IMMU-132 (10 mg/kg IV, days 1 and 8 every 21 days) or TPC from one of 4 prespecified single-agent regimens (capecitabine, eribulin, vinorelbine or gemcitabine). Pts continue treatment until progression requiring discontinuation or unacceptable toxicity. The primary endpoint is progression-free survival (PFS) and additional endpoints include overall survival (OS), ORR, DOR, safety and quality of life. Independent, blinded reads of scans will be performed.
Eligibility criteria: Adults &gt;18 yrs old, with metastatic breast cancer, triple-negative by most recent biopsy, measurable disease by CT or MRI as per RECIST1.1, ECOG performance score 0 or 1, adequate safety laboratories. Refractory/relapsed after ≥2 prior standard chemotherapy regimens for advanced disease, or &gt;1 therapy for pts who progress within 12 months of adjuvant therapy. Pts must have received taxane and be eligible by investigator to receive at least one of the TPC agents. Pts with treated, non-progressive brain metastases are eligible.
Specific aims: To compare IMMU-132 to TPC as measured by PFS, OS, ORR, DOR,QOL, adverse events, safety laboratories, incidence of dose delays and reductions, and treatment discontinuations due to toxicity.
Statistical methods: Assuming a median PFS of 3 mo. and OS of 10 mo. with TPC vs. 5 and 15 mo. with IMMU-132, respectively, a study size of 328 patients has &gt;95% and &gt;80% power to detect a statistically significant difference in PFS and OS, respectively, between the two treatment arms.
Present accrual and target accrual: Trial enrollment will begin prior to SABCS 2017 with approximately 328 patients expected to be enrolled over 18 months at approximately 100 institutions in North America, Europe and potentially elsewhere.
Contact: Immu132@Immunomedics.com
Citation Format: Bardia A, Rugo HS, Horne H, Wegener WA, Goldenberg DM, O'Shaughnessy J. A phase III, randomized trial of sacituzumab govitecan (IMMU-132) vs treatment of physician choice (TPC) for metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-07-05.