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

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. Table: 483TIPTabled 1TrialHistologyPlannedenrollmentExperimentalControlIMpower130Nonsquamous650Atezo +carboplatin + nab-paclitaxelCarboplatin + nab-paclitaxelIMpower131Squamous1025Atezo +carboplatin + paclitaxelAtezo +carboplatin + nab-paclitaxelCarboplatin + nab-paclitaxelIMpower132Nonsquamous568Atezo + carboplatinAtezo + cisplatin + pemetrexedCarboplatinCisplatin + pemetrexedIMpower150Nonsquamous1200Atezo +carboplatin + paclitaxelAtezo +carboplatin + paclitaxel + bevCarboplatin + paclitaxel + bev Open table in a new tab 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.