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 Cytotoxic agents
Breast Cancer
Immunotherapy
Therapy
Biological therapy
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.