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 Anticancer agents
Small Cell Lung Cancer
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.