483TiP - A Phase (Ph) III clinical program: 1L atezolizumab (atezo) plus chemotherapy (chemo) in chemo-naive advanced NSCLC

Date 18 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Anticancer agents
Non-Small-Cell Lung Cancer, Metastatic
Immunotherapy
Presenter Tony S.K. Mok
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors T.S.K. Mok1, R.M. Jotte2, F. Cappuzzo3, M. Reck4, V. Papadimitrakopoulou5, H.J. West6, A. Sandler7, S. Mocci7, S. Coleman8, T. Asakawa9, M.A. Socinski10
  • 1Clinical Oncology, The Chinese University of Hong Kong, n/a - Hong Kong/HK
  • 2N/a, Rocky Mountain Cancer Centers U.S. Oncology Network, 80218 - Denver/US
  • 3U.o. Oncologia Medica, Ospedale Civile - Istituto Toscano Tumori, 57100 - Livorno/IT
  • 4N/a, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf/DE
  • 5Department Of Thoracic/head And Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston/US
  • 6N/a, Swedish Cancer Institute, Seattle/US
  • 7Product Development Oncology, Genentech, Inc., South San Francisco/US
  • 8Product Development Oncology, Genentech, Inc, 94080 - South San Francisco/US
  • 9Biostatistics, Genentech, Inc, 94080 - South San Francisco/US
  • 10N/a, Florida Hospital Cancer Institute, Orlando/US

Abstract

Background

Atezo is an mAb that inhibits the interaction of PD-L1 with its receptors PD-1 and B7.1, thereby restoring tumor-specific T-cell immunity. Atezo monotherapy increases survival in patients (pts) with squamous (sq) and nonsquamous (nonsq) NSCLC across PD-L1 expression levels. The potential for chemo to further augment responses to atezo, with tolerable safety, has also been demonstrated. The inhibition of VEGF-mediated immunosuppression by bevacizumab (bev) may also enhance atezo efficacy for nonsq NSCLC. Four global, Ph III, randomized, open-label trials are being conducted to evaluate first-line (1L) atezo + platinum-based chemo ± bev in chemo-naive pts with stage IV NSCLC.

Trial design

Eligibility criteria include stage IV NSCLC, measurable disease (RECIST v1.1), no prior chemo, and ECOG PS 0-1. Exclusion criteria include untreated CNS metastases, autoimmune disease and prior exposure to immunotherapy. Pts will be enrolled regardless of PD-L1 expression status and randomized to the treatment arms. In IMpower130 (NCT02367781) and IMpower131 (NCT02367794), pts will be stratified by sex, liver metastases and centrally assessed PD-L1 expression by IHC. In IMpower132 (NCT02657434) pts will be stratified by sex, ECOG PS, type of chemo (carboplatin vs cisplatin) and smoking status. In IMpower150 (NCT02366143) pts will be stratified by sex, liver metastases and centrally-assessed PD-L1 expression by IHC. Pts will receive maintenance depending on their allocated treatment regimen. Pts receiving atezo may continue until loss of clinical benefit. Co-primary endpoints are PFS and OS. Secondary endpoints include ORR and safety. Evaluation of predictive biomarkers associated with efficacy will be performed.rn

Table: 483TIP

rnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrnrn
TrialHistologyPlanned enrollmentExperimentalControl
IMpower130Nonsquamous650Atezo + carboplatin + nab-paclitaxelCarboplatin + nab-paclitaxel
IMpower131Squamous1025Atezo + carboplatin + paclitaxelCarboplatin + nab-paclitaxel
Atezo + carboplatin + nab-paclitaxel
IMpower132Nonsquamous568Atezo + carboplatinCarboplatin
Atezo + cisplatin + pemetrexedCisplatin + pemetrexed
IMpower150Nonsquamous1200Atezo + carboplatin + paclitaxelCarboplatin + paclitaxel + bev
Atezo + carboplatin + paclitaxel + bev
rn

Clinical trial indentification

NCT02367781, NCT02367794, NCT02657434, NCT02366143

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. R.M. Jotte: Honoraria & Speakers Bureau: Eli Lilly, BMS. F. Cappuzzo: Honoraria: Roche, Clovis, Pfiser. Consulting or Advisory: Roche, Clovis, Pfizer, Lilly. M. Reck: Consulting/advisory role and Speaker Bureau for Roche, lIlly, BMS, MSD, AshaZ Zeneca, Pfizer, Boehringer Ingeleim, Celgene. V. Papadimitrakopoulou: Consulting or advisory role with Genentech, Gensignis Life Sciences, Janssen, Clovis Oncology, Biothera, Merck. Research funding with Clovis, Astra Zeneca, Merck, Janssen, Bayer. H.J. West: Consultant: AZ, BMS, Genentech/Roche, Merck Speaking: Genentech/Roche. A. Sandler, S. Mocci, T. Asakawa: Genentech employee. S. Coleman: Employment: Genentech Stock: Roche, Gilead Sciences, Celgene, Teva Travel, accomodations, expenses: Genentech. M.A. Socinski: Research support – Genentech Speaker’s Bureau – Genentech.