Phase III postneoadjuvant study evaluating sacituzumab govitecan, an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment: SASCIA.

person Frederik Marmé Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Mannheim, Germany info_outline Frederik Marmé, Elmar Stickeler, Jenny Furlanetto, Carsten Denkert, Marcus Schmidt, Mattea Reinisch, Toralf Reimer, Wolfgang Janni, Michael Untch, Bruno Valentin Sinn, Volker Moebus, Laura Michel, Laura Schoellhorn, Sabine Schmatloch, Julia Rey, Sibylle Loibl

Authors person Frederik Marmé Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Mannheim, Germany info_outline Frederik Marmé, Elmar Stickeler, Jenny Furlanetto, Carsten Denkert, Marcus Schmidt, Mattea Reinisch, Toralf Reimer, Wolfgang Janni, Michael Untch, Bruno Valentin Sinn, Volker Moebus, Laura Michel, Laura Schoellhorn, Sabine Schmatloch, Julia Rey, Sibylle Loibl Organizations Medical Faculty Mannheim, Heidelberg University, University Hospital Mannheim, Mannheim, Germany, Department of Gynecology and Obstetrics, Medical Faculty, RWTH Aachen University, Aachen, Germany, German Breast Group (GBG), Neu-Isenburg, Germany, Institute of Pathology, Philipps-University Marburg and University Hospital Marburg, Marburg, Germany, Department of Obstetrics and Gynecology University Hospital Mainz, Mainz, Germany, Breast Unit, Kliniken Essen Mitte, Essen, Germany, Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany, University of Ulm, Ulm, Germany, Helios Klinikum Berlin-Buch, Berlin, Germany, Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, Internal Medicine II, Dept. of Hematology & Oncology University of Frankfurt, Frankfurt, Germany, National Center for Tumor Disease, Heidelberg, Germany, Breast Center, St. Elisabeth Hospital, Kassel, Germany Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Gilead Sciences, Inc. Background: Women with triple-negative breast cancer (TNBC) having residual disease after neoadjuvant chemotherapy (NACT) as well as HR-positive/HER2-negative breast cancer (BC) with a CPS (clinical and post treatment pathological stage) +EG (estrogen receptor status and grade) score ≥ 3 or score 2 and nodal involvement after NACT (ypN+) are at high risk of recurrence. Sacituzumab govitecan is approved for the treatment of patients with metastatic TNBC who received at least two prior therapies for metastatic disease and has shown activity in heavily pretreated patients with metastatic HR-positive/HER2-negative BC. Therefore, sacituzumab govitecan may represent a new option against the resistant residual disease after standard NACT. Methods: SASCIA is a phase III, prospective, international, multi-center, randomized, open label, parallel group study in patients with HER2-negative BC with residual disease after NACT (NCT04595565). Eligible patients must have received taxane-based NACT for 16 weeks, including at least 6 weeks of a taxane. Patients should be at high risk of recurrence after treatment, defined as having centrally confirmed HER2-negative BC (IHC score 0-1 or FISH negative according to ASCO/CAP guideline) assessed preferably on tissue from postneoadjuvant residual invasive disease of the breast and either HR-negative (<1% positive stained cells), with any residual invasive disease > ypT1mi after NACT or HR-positive (≥1% positive stained cells), with a CPS+EG score ≥ 3 or CPS+EG score 2 and ypN+ using local ER and grade assessed on core biopsies taken before NACT. Radiotherapy should be delivered before the start of study treatment. Patients are randomized 1:1 to receive either sacituzumab govitecan 10 mg/kg body weight (days 1, 8 q3w for eight cycles) or treatment of physician´s choice (capecitabine 2000 mg/m² day 1-14 q21 or platinum-based chemotherapy i.e. carboplatin AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles or observation). Randomization is stratified by HR status (HR-positive vs negative) and nodal involvement after NACT (ypN+ vs ypN0). In patients with HR-positive BC, endocrine-based therapy will be administered according to local guidelines. The primary endpoint is invasive disease-free survival (iDFS). Secondary endpoints include comparison of overall survival (OS, key secondary endpoint), distant disease-free survival, locoregional recurrences-free interval, safety, compliance, iDFS and OS according to stratified and - predefined subgroups, patient reported outcome, and quality of life between treatment arms. As of February 2 2021, 7/1200 patients have been randomized in Germany. International study groups will join soon. Clinical trial information: NCT04595565