136TiP - IMpassion130: Phase III trial comparing 1L atezolizumab with nab-paclitaxel versus placebo with nab-paclitaxel in treatment-naive patients with mTNBC

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Cytotoxic agents
Breast Cancer, Metastatic
Immunotherapy
Presenter Leisha Emens
Citation Annals of Oncology (2016) 27 (suppl_9): ix35-ix41. 10.1093/annonc/mdw577
Authors L. Emens1, S. Adams2, S. Loi3, A. Schneeweiss4, H. Rugo5, E. Winer6, C. Barrios7, V. Dieras8, J. de la Haba-Rodriguez9, L. Gianni10, N. Kusuma11, S.Y. Chui12, P. Schmid13
  • 1Oncology, Johns Hopkins University School of Medicine, 21231-1000 - Baltimore/US
  • 2N/a, New York University School of Medicine, New York/US
  • 3Division Of Cancer Medicine, Peter MacCallum Cancer Center, 3002 - Melbourne/AU
  • 4Women’s Hospital, Heidelberg University Hospital, 69120 - Heidelberg/DE
  • 5N/a, University of California San Francisco Comprehensive Cancer Center, San Francisco/US
  • 6N/a, Dana-Farber Cancer Institute, Boston/US
  • 7Department Of Medicine, PUCRS School of Medicine, Porto Alegre/BR
  • 8Medical Oncology, Institut Curie, 75248 - Paris/FR
  • 9N/a, Hospital Universitario Reina Sofía, Cordoba/ES
  • 10N/a, San Raffaele Scientific Institute, Milan/IT
  • 11N/a, Roche Singapore Pte Ltd., Singapore/SG
  • 12N/a, Genentech, Inc., South San Francisco/US
  • 13N/a, Barts Cancer Institute-Queen Mary University of London, London/GB

Abstract

Background

Chemotherapy remains the mainstay therapy for metastatic triple-negative breast cancer (mTNBC) but offers limited clinical benefit at the expense of significant toxicity. This underscores the need for new treatment options. Atezolizumab (atezo) is a mAb specific for PD-L1 that prevents PD-L1 binding to its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. TNBC is a rational target indication for atezo due to PD-L1 expression on tumor-infiltrating immune cells (IC), and a high mutation burden that may generate immunogenic neoantigens. Atezo monotherapy was well tolerated and produced durable responses in patients (pts) with mTNBC (Emens et al 2015). Promising activity observed in pts treated with atezo plus nab-paclitaxel (nab-pac) supports the hypothesis that the combination may represent an effective new treatment option for pts with mTNBC (Adams et al 2016). IMpassion130 (NCT02425891), a global Phase III randomized, multicenter, placebo-controlled clinical trial, is being conducted to evaluate the efficacy and safety of first-line (1L) atezo + nab-pac compared with placebo + nab-pac alone in treatment-naive pts with mTNBC.

Trial design

Eligibility criteria include locally advanced or metastatic TNBC, no prior systemic treatment for advanced TNBC, measurable disease per RECIST v1.1, and ECOG PS 0-1. Exclusion criteria include untreated CNS metastases (asymptomatic treated CNS metastases permitted), prior exposure to immunotherapy and autoimmune disease. Pts are randomized 1:1 to receive atezo (840 mg q2w) or placebo on days 1 and 15, along with nab-pac (days 1, 8 and 15) in 28-day cycles. Stratification factors include presence of liver metastases, prior taxane therapy and PD-L1 expression < 1% vs ≥ 1% of IC (IC0 vs IC1/2/3 with VENTANA SP142 IHC assay). Co-primary endpoints of PFS and OS will be evaluated in the ITT population and in PD-L1–selected pts. Secondary endpoints include ORR and safety. Tumor biopsies obtained at baseline and disease progression will be assessed for biomarkers associated with responses to atezo and immune escape. Approximately 900 pts will be enrolled.

Clinical trial indentification

NCT02425891

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd

Funding

F. Hoffmann-La Roche Ltd

Disclosure

L. Emens: Honoraria/Consulting: Celgene, Amgen, Syndax, Vaccinex, Astrazeneca, Amgen, Research funding: Roche, Genentech, Astrazeneca, Serone, Maxcyte, Amplimmune. patent, royaties, Aduco Biotech-minor. Advisory Communitee FDA Cell Tissue and gene therapies. S. Adams: Genentech and Merck -Research funding. A. Schneeweiss: Honararia: Celgene, Roche; Research funding: Celgene. E. Winer: McKinsey honorarium for consulting Gerson Lehman honorarium for consulting Verastem honorarium for scientific advisory board. C. Barrios: Honararia/Consulting: BI, GSK, Novartis, Pfizer, Roche, Eisai, Bioepis, Amgen; Research funding: Amgen, AZ, BI, GSK, Novartis, Pfizer, Roche, Eisai, Lilly, Sanofi, Celgene, Taiho, Mylan, Merrimack, Merck, Abbvie, Astellas, Daichi-Sankyo, Biomarin, BMS. V. Dieras: Consulting/advisory: Roche, Novartis, Pfizer, Elsai Speakers\' Bureau: Roche, Novartis, Pfizer Travel, accommodations, expenses, Roche, Novartis, Pfizer. J. de la Haba-Rodriguez: Honoraria- Roche Pharma AG Consulting or advisory role- Roche Pharma AG Research funding- yes- Roche Pharma AG. L. Gianni: Consulting & Travel: Roche, GSK, Pfizer, BI, Celgene, Tahio Pharma, Tiziana Pharma, Synthon, AZ, Genomic Health, Merck Sharp & Dohme, Synafflix. N. Kusuma: Employee of Roche Singapore Pte Ltd. S.Y. Chui: Genentech Employee, Research funding from Genentech/Roche. P. Schmid: Honoraria-AZ, Pfizer Consulting/advisory role - Roche/Genentech Research funding-Genentech, AZ, Astellas, OncoGenex. All other authors have declared no conflicts of interest.