Background: This phase 1b study investigated safety and activity of combined checkpoint inhibition (CPI) with programmed death-ligand 1 (PD-L1) antibody atezolizumab plus cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in NSCLC.
Patients and methods: Eligible patients had previously treated locally advanced or metastatic non-small cell lung cancer (NSCLC) or melanoma. A standard 3+3 dose escalation investigated atezolizumab (600-1200 mg IV every 3 weeks) plus ipilimumab starting at 1 mg/kg, administered as a single dose or 4 doses, administered every 3 weeks. The expansion stage included a cohort previously treated with atezolizumab. Patients were monitored for safety and tolerability; response was evaluated every 6 weeks.
Results: Twenty-seven patients were enrolled, 4 with melanoma and 23 with NSCLC; here, we focus on data for the NSCLC population. Three of 23 patients (13.0%) received prior CPI. No dose-limiting toxicities were reported during dose escalation; dose expansion occurred with atezolizumab 1200 mg plus 1 cycle of ipilimumab 1 mg/kg. Most common treatment-emergent adverse events were dyspnea (39%) and cough (35%); treatment-related Grade ≥3 adverse events occurred in 11 patients (48%), most frequently pneumonitis (17%) and amylase or lipase elevation (9% each). Six of 23 NSCLC patients (26%) achieved confirmed responses, 5 of whom (25%) were CPI naive. Median duration of response was 23.0 (95% CI, 3.2-36.9) months overall and 36.9 (95% CI, 2.9-36.9) months in CPI-naive patients.
Conclusion: Preliminary efficacy of atezolizumab plus ipilimumab was observed in metastatic NSCLC. The combination had manageable toxicity, with a safety profile consistent with those of the individual agents.
Keywords: CTLA-4; Checkpoint inhibition; Immunotherapy; PD-L1; Previously treated NSCLC.
Copyright © 2021. Published by Elsevier Inc.