480TiP IMpower110: Phase III study on 1L atezolizumab (atezo) in PD-L1–selected chemotherapy (chemo)-naive NSCLC patients (pts)

Abstract

Background: For pts with advanced NSCLC without genetic driver alterations, a number of first-line (1L) standard of care chemo regimens are available for nonsquamous (nonsq) and squamous (sq) histology, and remain the main 1L options despite poor survival and toxicities. Immunotherapies targeting PD-L1/PD-1 are now available for 2L+ NSCLC but their benefits remain to be fully studied in 1L setting. Atezo, an anti-PD-L1 mAb, prevents PD-L1 interacting with PD-1 and B7.1 restoring tumor-specific T-cell immunity. Atezo has shown durable responses and survival benefit in NSCLC that increases with higher PD-L1 expression on tumor cells (TC) and/or tumor-infiltrating immune cells (IC) in Phase I/II trials. IMpower110 (NCT02409342), a global Phase III randomized, multicenter, open-label trial, will evaluate efficacy and safety of 1L atezo vs cisplatin (cis)/carboplatin (carbo) + pemetrexed (pem) or gemcitabine (gem) in PD-L1-selected chemo-naive pts with advanced nonsq or sq NSCLC, respectively. Trial design: Eligibility criteria include stage IV nonsq or sq NSCLC, measurable disease (RECIST v1.1), ECOG PS 0-1, no prior chemotherapy for advanced NSCLC and centrally-assessed PD-L1 expression ≥ 1% on TC or IC (TC1/2/3 or IC1/2/3 with VENTANA SP142 IHC assay; expected prevalence, ≈ 65%). Exclusion criteria include active or untreated CNS metastases, prior immune checkpoint blockade therapy or autoimmune disease. Pts will be randomized 1:1 to receive atezo or cis/carbo + pem (nonsq)/gem (sq) for 4 or 6 21-day cycles. Pts in comparator arms can receive pem (nonsq)/best supportive care (sq) until disease progression. Pts receiving atezo may continue until loss of clinical benefit. Stratification factors include sex, ECOG PS, histology (nonsq vs sq), and centrally assessed PD-L1 expression by IHC. Co-primary endpoints are PFS and OS. Key secondary endpoints are ORR, DOR, IRF-assessed PFS (RECIST v1.1) and TTD. Safety and PK will also be evaluated. Tumor biopsies at RECIST v1.1 progression will be assessed for immunologic biomarkers associated with responses to atezo and to differentiate non-conventional responses from radiographic progression. Approximately 570 pts will be enrolled.