212TiP - IMpassion031: A phase III study comparing neoadjuvant atezolizumab (atezo) vs placebo in combination with anthracycline/nab-paclitaxel (nab-pac)–ba...

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Breast Cancer
Cancer Immunology and Immunotherapy
Presenter Elizabeth Ann Mittendorf
Citation Annals of Oncology (2017) 28 (suppl_5): v43-v67. 10.1093/annonc/mdx362
Authors E.A. Mittendorf1, C.H. Barrios2, N. Harbeck3, K.H. Jung4, D. Miles5, S. Saji6, H. Zhang1, A. Duc7, S. Rafii8, C. Lai9
  • 1Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, 77030 - Houston/US
  • 2Department Of Medicine, PUCRS School of Medicine, Porto Alegre/BR
  • 3Breast Center, University of Munich (LMU), Munich/DE
  • 4Department Of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul/KP
  • 5Medical Oncoloy, Mount Vernon Cancer Centre, Northwood/GB
  • 6Medical Oncology, Fukushima Medical University, School of Medicine, Fukushima/JP
  • 7Biostatistics, F. Hoffmann-La Roche Ltd., Basel/CH
  • 8Global Oncology Product Development, F. Hoffmann-La Roche AG, Welwyn Garden City/GB
  • 9Global Development, Genentech, South San Francisco/US

Abstract

Background

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.

Trial design

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.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

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.