Abstract OT1-01-01: IMpassion131: A phase III study comparing 1L atezolizumab with paclitaxel vs placebo with paclitaxel in treatment-naive patients with inoperable locally advanced or metastatic triple negative breast cancer (TNBC)
Authors: Miles D , André F , Gligorov J , Verma S , Xu B , Cameron D , Barrios CH , Schneeweiss A , Easton V , Ghazi Y , O'Shaughnessy J 
Published: February 2018

Abstract
Background: Chemotherapy (including paclitaxel) remains the predominant treatment for metastatic TNBC but clinical outcomes remain poor. Therefore, new therapeutic approaches are needed. Atezolizumab blocks the binding of PD-L1 to its receptors PD-1 and B7.1, thus restoring tumor-specific T cell immunity. TNBC is a rational target for atezolizumab therapy due to high PD-L1 expression on tumor-infiltrating immune cells (IC) and elevated T cell tumor infiltration. Furthermore, combining chemotherapy with atezolizumab is hypothesized to enhance anti-tumor immune response via neoantigen release. Atezolizumab alone and in combination with nab-paclitaxel has demonstrated promising clinical benefit in metastatic TNBC and was well tolerated, with no exacerbation of chemotherapy-associated adverse events. Atezolizumab in combination with nab-paclitaxel is being further investigated as 1L TNBC treatment in IMpassion130. IMpassion131 is a global, multi-center, randomized, double-blind, placebo-controlled study comparing the efficacy and safety of 1L atezolizumab + paclitaxel vs placebo + paclitaxel in patients with untreated, inoperable, locally advanced or metastatic TNBC. (NCT03125902)
Methods: Eligibility criteria include patients with inoperable, locally advanced or metastatic TNBC, histologically confirmed; de novo or recurrent disease after early breast cancer treated with chemotherapy ≥ 12 months prior; eligible for taxane monotherapy; no prior chemotherapy or targeted systemic therapy for inoperable locally advanced or metastatic disease; ECOG PS 0-1 and measurable disease by RECIST v1.1. Exclusion criteria include known symptomatic CNS disease, prior immunotherapy and a history of autoimmune disease. Approximately 495 patients will be randomized 2:1 to receive atezolizumab (840 mg) or placebo (q2w; days 1 and 15 of 28-day cycle) plus paclitaxel (90 mg/m2; days 1, 8, 15 of 28-day cycle) until disease progression. Stratification factors are PD-L1 expression on tumor-infiltrating IC (IC0 &lt; 1% vs IC1/2/3 ≥ 1% with VENTANA SP142 IHC assay), prior taxane therapy, presence of liver metastases and geographical region. The primary endpoint is progression-free survival (PFS) measured by RECIST v1.1. Key secondary endpoints include overall survival (OS), 12- and 18-month OS rates, 12-month PFS rate, objective response rate, duration of response, and safety. Tumor biopsies will be collected at baseline, on treatment and at disease progression to assess for biomarkers of treatment response and immune escape.
Citation Format: Miles D, André F, Gligorov J, Verma S, Xu B, Cameron D, Barrios CH, Schneeweiss A, Easton V, Ghazi Y, O'Shaughnessy J. IMpassion131: A phase III study comparing 1L atezolizumab with paclitaxel vs placebo with paclitaxel in treatment-naive patients with inoperable locally advanced or metastatic 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 OT1-01-01.