521TiP - IMpower133: A phase I/III study of atezolizumab (atezo) with carboplatin (carbo) and etoposide as 1L therapy in patients (pts) with extensive-stage...

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anti-Cancer Agents & Biologic Therapy
Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Presenter Tony S.K. Mok
Citation Annals of Oncology (2016) 27 (suppl_9): ix169-ix169. 10.1093/annonc/mdw598
Authors T.S.K. Mok1, L. Horn2, M. Reck3, M.L. Johnson4, X. Tang5, S. Lam6, D.S. Shames7, D. Waterkamp6, A. Lopez-Chavez6, A. Sandler8, G. Giaccone9, S.V. Liu10
  • 1Clinical Oncology, The Chinese University of Hong Kong, n/a - Hong Kong/HK
  • 2Department Of Medicine, Vanderbilt Ingram Cancer Center, 37232-6307 - Nashville/US
  • 3N/a, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf/DE
  • 4Tennessee Oncology, Sarah Cannon Research Institute, Nashville/US
  • 5Pdbb, F. Hoffmann-La Roche Ltd, Shanghai/CN
  • 6Product Development Oncology, Genentech, Inc., 94080 - South San Francisco/US
  • 7Oncology Biomarker Development, Genentech, Inc., 94080 - South San Francisco/US
  • 8Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 9Lombardi Comprehensive Cancer Center, Georgetown University, Washington/US
  • 10Medical Oncology, Lombardi Cancer Center Georgetown University, Washington/US

Abstract

Background

Platinum-based chemotherapy (chemo) with etoposide is the current first-line (1L) standard of care for the majority of pts with ES-SCLC. Although initial response rates with chemo range from 50% to 70%, survival outcomes remain poor (median OS, < 1 year), highlighting the need for new treatments. Atezo, an anti–PD-L1 mAb that prevents the interaction of PD-L1 with its receptors PD-1 and B7.1, restores antitumor T-cell activity and has shown tolerable safety with promising durability of response in pts with ES-SCLC: confirmed ORR was 6% (n = 1/17 [partial response]; DOR of 7 mo) by RECIST v1.1 and 24% by immune-related response criteria (irRC; n = 4/17, with 2 pts on atezo for ≥ 12 mo). Preliminary data also indicate the potential synergism of atezo with platinum-based chemo in NSCLC, in which durable responses may translate into improved survival over atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial was initiated to evaluate the efficacy and safety of 1L atezo + carbo + etoposide compared with placebo + carbo + etoposide in treatment-naive pts with ES-SCLC.

Trial design

Inclusion criteria include ES-SCLC, measurable disease (RECIST v1.1), ECOG PS 0-1 and no prior anticancer treatment. Exclusion criteria include untreated CNS metastases and autoimmune disease. Submission of tumor tissue is a study requirement but not mandatory for entry; pts will be enrolled regardless of biomarker status. Stratification factors include sex, ECOG performance status and presence of brain metastases. Eligible pts will be randomized 1:1 to receive four 21-day cycles of atezo (1200 mg IV) or placebo in combination with carbo (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2, d 1-3), followed by maintenance therapy with atezo or placebo until PD per RECIST v1.1. Pts can continue with treatment until persistent radiographic PD, symptomatic deterioration or unacceptable toxicity. Co-primary endpoints are investigator-assessed PFS per RECIST v1.1 and OS. Secondary efficacy endpoints include ORR and DOR. Safety and tolerability will also be assessed; ≈ 400 pts will be enrolled.

Clinical trial indentification

NCT02763579

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd

Funding

F. Hoffmann-La Roche Ltd

Disclosure

T.S.K. Mok: Chinese University of Hong Kong employee; Sanomics Ltd stocks; AZ, Roche, Lily, Merck, MSD, BMS, BI, Novartis, Clovis, Amgen, Janssen, AVEO, Biodesix, Prime Oncology, ACEA Biosciences, Vertex, SFJ, GSK, Biomarin, Pfizer, Genedecode funding/consulting. L. Horn: Research: AZ Consulting: Bayer, BI, BMS, Genentech, Lilly, Merck and Xcovery. M. Reck: Consulting/advisory role and Speaker Bureau for Roche, lIlly, BMS, MSD, AshaZ Zeneca, Pfizer, Boehringer Ingeleim, Celgene. X. Tang: Roche employee. S. Lam: Genentech employee; own Roche stock. D.S. Shames, A. Lopez-Chavez, A. Sandler: Genentech employee. D. Waterkamp: Roche stocks. Roche/Genentech employee. G. Giaccone: Consulting or Advisory Role: Clovis, Boehringer- Ingelheim; Celgene Research grants: Karyopharm, Astra-Zeneca; Eli-Lilly. S.V. Liu: Consulting or Advisory Role: Genentech, Boehringer Ingelheim, Ariad, Biodesix, Perthera. All other authors have declared no conflicts of interest.