Phase III clinical trials in chemotherapy-naive patients with advanced NSCLC assessing the combination of atezolizumab and chemotherapy

Background

Current treatments for advanced NSCLC include platinum (plat)-based doublet chemotherapy (chemo), pemetrexed (pem), bevacizumab, targeted drugs and programmed death-ligand 1 (PD-L1)/PD-1–targeted immunotherapy. Atezolizumab (atezo; anti-PDL1) inhibits binding of PD-L1 to PD-1 and B7.1 and restores anti-tumor T-cell activity. Clinical efficacy and survival rates with atezo monotherapy increase with increasing PD-L1 levels on tumor cells (TC) and tumor infiltrating immune cells (IC) in patients with advanced NSCLC. A phase Ib study revealed the potential for chemo to further enhance responses to atezo with tolerable safety in pts, across PD-L1 expression levels. The combination of atezo and chemo is now being examined in phase III studies.

Trial design

Three phase III randomized, multicenter, open-label studies are assessing plat-based chemo + atezo or plat-based chemo + atezo + pem as 1L therapy in chemo-naive pts with advanced NSCLC (Table). Pts will be enrolled regardless of PD-L1 status and must have previously untreated stage IV NSCLC. Inclusion criteria include measurable disease per RECIST v1.1 and ECOG PS 0-1; pts with untreated CNS metastases, autoimmune disease or prior immunotherapy will be excluded. Stratification factors will include sex and ECOG status. Archival tumor or biopsy sample will be obtained at screening. In IMpower130 and 131, pts will be randomized to receive atezo 1200 mg with standard plat-based chemotherapy for 4 or 6 21-day cycles, then maintenance with atezo. In IMpower132, pts will receive atezo 1200 mg q3w + plat-based chemo + pem, then maintenance with atezo + pem. Endpoints include OS, PFS, ORR, DOR, safety, PK and QOL. Tumor biopsies at RECIST v1.1 progression will be assessed to distinguish pseudoprogression/tumor-immune infiltration from actual progression and to evaluate biomarkers associated with response and immune escape.

Clinical trial identification

IMpower130: NCT02367781 IMpower131: NCT02367794 IMpower132: NCT02657434

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

M. Reck: Consulting/advisory role and Speaker Bureau for Roche, Lilly, BMS, MSD, Astra Zeneca, Pfizer, Boehringer Ingeleim, Celgene. V.A. Papadimitrakopoulou: Consulting or advisory role with Genentech, Gensignis Life Sciences, Janssen, Clovis Oncology, Biothera, Merck. Research funding with Clovis, Astra Zeneca, Merck, Janssen, Bayer. F. Cappuzzo: Honoraria: Roche, Clovis, Pfizer. Consulting or Advisory: Roche, Clovis, Pfizer, Lilly. R. Jotte: Honoraria & Speakers Bureau: Eli Lilly, BMS. T.S.K. Mok: Leadership/stock: Sanomics, Honoraria/Consulting includes: AZ, Roche, Lily, Merck, MSD, BMS, BI, Novartis, Clovis, Amgen, Janssen, AVEO, Biodesix, Prime, ACEA Biosciences, Vertex, SFJ, GSK, Biomarin, Pfizer, vertex, SFS, ACFA, Biosciences, Genedecode. A. Sandler: Genentech employee, Compensated Consultant role for Genentech/Roche, Genentech/Roche stock, Honoraria recipient from Genentech/Roche, Genentech research funding paid to institution, Provided compensated expert testimony for Genentech/Roche. D. Waterkamp: Roche/Genentech employee. S. Coleman: Employment: Genentech Stock: Roche, Gilead Sciences, Celgene, Teva. T. Asakawa: Genentech employee. M. Socinski: Research support – Genentech Speaker's Bureau – Genentech.