58TiP - IMpower133: Phase I/III trial of first-line atezolizumab with carboplatin and etoposide in ES-SCLC

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Small-Cell Lung Cancer
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Martin Reck
Citation Annals of Oncology (2017) 28 (suppl_2): ii17-ii20. 10.1093/annonc/mdx088
Authors M. Reck1, A.S. Mansfield2, S.V. Liu3, T.S.K. Mok4, X. Tang5, S. Lam6, F. Kabbinavar6, A. Lopez-Chavez6, A. Sandler6, L. Horn7
  • 1Lung Clinic, Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 2Division Of Medical Oncology, Mayo Clinic, 55905 - Rochester/US
  • 3Lombardi Comprehensive Cancer Center, Georgetown University, Washington/US
  • 4The Chinese University of Hong Kong, Hong Kong/CN
  • 5F. Hoffmann-La Roche Ltd, Basel/CH
  • 6Genentech, Inc., South San Francisco/US
  • 7Department Of Medicine, Vanderbilt Ingram Cancer Center, Nashville/US

Abstract

Background

Platinum-based chemotherapy (chemo) with etoposide is the current first-line standard of care for the majority of patients (pts) with ES-SCLC. However, survival outcomes remain poor (median OS, < 1 year) despite initial response rates ranging from 50%-70%. Atezolizumab (atezo) is an anti–PD-L1 mAb that prevents the interaction of PD-L1 with its receptors, PD-1 and B7.1, and restores antitumor T-cell activity. Tolerable safety with promising durability of response has been shown with atezo 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 synergy between atezo and platinum-based chemo in NSCLC whereby durable responses may translate into improved survival compared with atezo alone. IMpower133 (NCT02763579), a global, Phase I/III, randomized, multicenter, double-blinded, placebo-controlled trial, will evaluate the efficacy and safety of 1L atezo + carboplatin + etoposide compared with placebo + carboplatin + etoposide in treatment-naive pts with ES-SCLC.

Trial design

Eligibility criteria include ES-SCLC, measurable disease (RECIST v1.1), ECOG PS 0-1 and no prior systemic anticancer treatment. Exclusion criteria include untreated CNS metastases and history of autoimmune disease. Submission of tumor tissue is a study requirement but pts will be enrolled regardless of biomarker status. Stratification factors are sex, ECOG performance status and presence of treated 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 carboplatin (AUC 5 mg/mL/min IV, d 1) and etoposide (100 mg/m2 IV, 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 investigator-assessed ORR and DOR. Safety and tolerability will also be assessed. Approximately 400 pts will be enrolled.

Clinical trial identification

NCT02763579

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd/Genentech Inc.

Funding

F. Hoffmann-La Roche Ltd/Genentech Inc.

Disclosure

M. Reck: Honoraria for lectures and consultancy with Boehringer-Ingelheim, Hoffmann-La Roche, Lilly, MSD, BMS, AstraZeneca, Celgene, Merck, Pfizer. A.S. Mansfield: Advisory Board: Genentech, BMS, and Trovagene. S.V. Liu: Advisory board/consultant for: Genentech, Pfizer, Ariad, Celgene, Boehringer Ingelheim, Lilly. T.S.K. Mok: Grant/Speaker/AdBoards: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis, BMS, Eisai, Taiho, Lilly, Merck, ACEA, Vertex, BMS, geneDecode, OncoGenex, Celgene, Ignyta, Taiho; Stock: Sanomics; Board: IASLC, CLCRF, CSCO, HKCTS. X. Tang: Roche employee. S. Lam: Roche/Genentech: employee, stock. F. Kabbinavar, A. Lopez-Chavez, A. Sandler: Employee, stock: Roche/Genentech. L. Horn: Advisory board: Genentech; Consulting: Abbvie, Merck, Lilly, Xcovery and EMD Serono.