122TiPGeparDouze/NSABP B-59: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy with atezolizumab or placebo in patients with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo

Background: In TNBC neoadjuvant chemotherapy (NACT) is associated with increased pathological complete response (pCR). Thus, patients with a pCR have a favourable prognosis. However, patients with residual disease have a substantially increased risk of recurrence compared to those with other subtypes of breast cancer (Liedtke 2008, Loibl 2017). Blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy (Adams 2017, Schmid 2017). Trial design: GeparDouze (NCT03281954/NSABP B-59/GBG96) is a phase III, double blind, placebo-controlled trial evaluating neoadjuvant administration of atezolizumab with NACT followed by adjuvant atezolizumab in patients with high risk TNBC. Accrual will be 1,520 randomized patients stratified by region (North America; Europe), tumor size (1.1-3.0 cm; > 3.0 cm), epirubicin or doxorubicin/cyclophosphamide (EC; AC) schedule (q2w; q3w), and nodal status (positive; negative). Patients are randomized 1:1 to receive atezolizumab 1200 mg or placebo IV every 3 weeks concurrently with sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses and every 3 week carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 weeks (per investigator discretion) for 4 cycles. Following surgery, patients resume atezolizumab 1200 mg or placebo IV every 3 weeks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Patients with centrally-confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines can be enrolled. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. Co-primary endpoints are event-free survival and pCR (ypT0/Tis ypN0). Main secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. GeparDouze is performed as an academic collaboration between NSABP and GBG. Clinical trial identification: NCT03281954; NSABP B-59; GBG96. Legal entity responsible for the study: NSABP and GBG. Funding: Genentech/Roche. Disclosure: S. Loibl: Grant: Roche; Grants: Pfizer, Celgene, Amgen outside of the submitted work. C. Jackisch: Personal fees: Roche; Personal fees: Celgene, during the conduct of the study. P. Rastogi: Grants: Genentech/Roche, during the conduct of the study; Other: AstraZeneca, Other: Genentech/Roche; Other: Lilly, outside the submitted work. P.C. Lucas: Grants: Genentech, during the conduct of the study; Other: Amgen; Personal fees: Bayer/Loxo, outside the submitted work. C. Denkert: Shareholder and co-founder: Sividon Diagnostics; Honoraria/consultation: Teva, Novartis, Pfizer, Roche, Amgen, MSD, Daiichi, Celgene, AstraZeneca; Patent application: EP18209672 - Cancer immunotherapy. J. Costantino: Grants: Genentech, during the conduct of the study. N. Wolmark: Service contract between NSABP Foundation, Inc. and Genentech/Roche during the conduct of the study. C. Geyer: Grants: Genentech/Roche, during the conduct of the study; Grants, non-financial support: AstraZeneca, AbbVie; Personal fees: Celgene; Grants, non-financial support: Genentech/Roche, outside the submitted work. All other authors have declared no conflicts of interest.