Abstract OT2-07-03: IMpassion031: A phase III study comparing neoadjuvant atezolizumab vs placebo in combination with nab-paclitaxel–based chemotherapy in early triple-negative breast cancer (TNBC)
Authors: Mittendorf E , Barrios CH , Harbeck N , Miles D , Saji S , Zhang H , Duc A-N , Rafii S , Lai C 
Published: February 2018

Abstract
Background Atezolizumab is an anti–programmed death-ligand 1 (PD-L1) monoclonal antibody that blocks the binding of PD-L1 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), high levels of tumor-infiltrating lymphocytes (TILs), and a higher mutation rate compared with other breast cancers suggesting a therapeutic opportunity for atezolizumab. Atezolizumab alone and in combination with nab-paclitaxel is well tolerated, with promising clinical activity in metastatic TNBC. Furthermore, cytotoxic chemotherapies like nab-paclitaxel can enhance anti-tumor immune responses via neoantigen release. Taken together, this supports the investigation of atezolizumab in combination with nab-paclitaxel in early-stage TNBC. IMpassion031 is a global Phase III, double-blind, randomized, multicenter, placebo-controlled study being conducted to evaluate the efficacy and safety of neoadjuvant treatment with nab-paclitaxel → doxorubicin + cyclophosphamide and either atezolizumab or placebo in invasive stage II/III early TNBC. The selection and sequence of chemotherapy has been chosen to maximize the opportunity for a robust immune response.
Methods: Eligible patients are those with previously untreated, central laboratory–confirmed invasive TNBC with primary tumor size &gt; 2 cm and ECOG PS 0-1. Exclusion criteria include history of invasive breast cancer, stage IV disease, bilateral breast cancer, prior systemic therapy for the treatment or prevention of breast cancer, prior immunotherapy and a history of autoimmune disease. Approximately 204 patients will be randomized 1:1 to receive atezolizumab (840 mg q2w) or placebo with nab-paclitaxel (125 mg/m2 qw) for 12 weeks. Subsequent atezolizumab (840 mg q2w) or placebo with doxorubicin (60 mg/m2 q2w) + cyclophosphamide (600 mg/m2 q2w) will be given for 4 cycles prior to surgery. Post-surgery, patients will be unblinded. Patients in the atezolizumab arm will continue to receive atezolizumab (1200 mg q3w × 11 doses) post-surgery. Stratification factors include stage II vs III TNBC at diagnosis and PD-L1 expression on tumor-infiltrating IC (IC0 &lt; 1% vs IC1/2/3 ≥ 1% with the VENTANA SP142 IHC assay). The primary endpoint is pathologic complete response (pCR); key secondary endpoints include pCR according to PD-L1 IC status, patient-reported outcomes, event-free survival and overall survival. Tumor samples will be taken at baseline, on treatment (optional), at surgery and post-recurrence for the assessment of biomarkers associated with treatment response and immune escape. (NCT pending).
Citation Format: Mittendorf E, Barrios CH, Harbeck N, Miles D, Saji S, Zhang H, Duc A-N, Rafii S, Lai C. IMpassion031: A phase III study comparing neoadjuvant atezolizumab vs placebo in combination with nab-paclitaxel–based chemotherapy in early triple-negative breast cancer (TNBC) [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 OT2-07-03.