Atezo is an anti–programmed death-ligand 1 (PD-L1) monoclonal antibody that prevents PD-L1 from binding to PD-1 and B7.1 receptors, thereby restoring tumor-specific immunity. TNBC is characterized by PD-L1 expression on tumor-infiltrating immune cells (IC), a high mutation rate and high levels of tumor-infiltrating lymphocytes (TILs), suggesting a therapeutic opportunity for atezo. Atezo alone and in combination with nab-pac is well tolerated, with promising activity in metastatic TNBC, supporting its investigation in early-stage disease. IMpassion031, a global Phase III, double-blind, randomized, multicenter, placebo-controlled study, is being conducted to evaluate the efficacy and safety of neoadjuvant treatment with nab-pac → doxorubicin + cyclophosphamide and either atezo or placebo in invasive stage II/III eTNBC. The choice and sequence of chemotherapy is selected to maximize the opportunity to establish a robust immune response.
Patients (pts) with previously untreated, central laboratory–confirmed invasive TNBC with primary tumor size > 2 cm and ECOG PS 0-1 are eligible. Exclusion criteria include history of invasive BC, stage IV disease, and prior immunotherapy or autoimmune disease. Approximately 204 pts will be randomized 1:1 to receive atezo (840 mg q2w) or placebo with nab-pac (125 mg/m2 qw) for 12 weeks, followed by atezo (840 mg q2w) or placebo with doxorubicin (60 mg/m2 q2w) + cyclophosphamide (600 mg/m2 q2w) for 4 cycles before surgery. Pts will be unblinded post-surgery and pts in the atezo arm will continue to receive atezo (1200 mg q3w × 11 doses). Stratification factors include stage II vs III at diagnosis and PD-L1 expression (IC0 vs IC1/2/3). The primary endpoint is pathological CR (pCR); key secondary endpoints include pCR according to PD-L1 status, pt-reported outcomes, event-free survival and overall survival. Tumor samples will be taken at baseline, on treatment (optional), at surgery and post-recurrence and will be assessed for biomarkers associated with responses and immune escape.
Clinical trial identification
NCT number available on poster
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
E.A. Mittendorf: Financial support to the institution from the following to conduct clinical trials that I serve as the Principal Investigator for: AstraZeneca, EMD Serono, Galena BioPharma, Genentech. Does not personally receive any funding. C.H. Barrios: Research: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Sanofi, GSK, Taiho, Mylan, Merrimack, Merck, Astellas, Bristol-Myers Squibb. Consulting: Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche-Genentech, Eisai. N. Harbeck: My COI is available for ESMO on their internal website. D. Miles: Honoraria for Advisory Boards from Roche-Genentech. S. Saji: Honoraria from AstraZeneca, Chugai Pharmaceutical, Eisai, Novartis Pharma, and research funds from AstraZeneca and Chugai Pharmaceutical. H. Zhang: Consultant for Genentech/Roche from 2015. A-N. Duc: Roche employee and stock. S. Rafii: Employed by Roche. C. Lai: Currently employed by Genentech/Roche and hold company stock. All other authors have declared no conflicts of interest.