Investigating denosumab as an add-on neoadjuvant treatment for RANK/L-positive or RANK/L-negative primary breast cancer and two different nab-paclitaxel schedules: 2x2 factorial design (GeparX)—An iterim safety analysis.

569Background: The GeparX study aims to investigate whether denosumab, an antibody targeting RANKL, increases the pCR rate when added to an anthracycline/taxane containing neoadjuvant chemotherapy (NACT) in patients (pts) with primary breast cancer (BC). Methods: GeparX enrolles pts with primary BC cT1c-cT4d, after central assessment of HER2, HR, TILs, Ki67. 778 pts will be randomized to NACT+/-denosumab (120mg s.c. q4w for 6 cycles), stratified by lymphocyte predominant BC (LPBC, ≤50% vs > 50%), subtype (HER2-/HR+ vs triple negative (TNBC) vs HER2+), and epirubicin/cyclophosphamide schedule (EC, q2w vs q3w). Secondarily, pts are randomized to different nab-paclitaxel schedules (nP): nP 125mg/m² weekly or nP 125mg/m² day 1,8 q22 followed by EC. Pts with TNBC receive carboplatin (AUC 2) and with HER2+ BC ABP 980 (trastuzumab biosimilar)+pertuzumab. Co-primary objectives compare the pCR (ypT0 ypN0) rates of NACT+/-denosumab and the pCR rates between nP 125 weekly and nP 125 d1,8 q22. Secondary objectives ar...