Brief Report: Phase II Clinical Trial of Atezolizumab in Advanced Nonsmall Cell Lung Cancer Patients Previously Treated With PD-1-Directed Therapy

Background:: Prospective data of sequencing PD-L1 inhibition after PD-1 inhibition is limited in non-small cell lung cancer (NSCLC). We report a phase II clinical trial of atezolizumab following PD-1 directed therapy (NCT03014648).

Methods:: Previously treated advanced NSCLC patients were enrolled in cohorts based on response to prior nivolumab or pembrolizumab therapy; progressive disease (Cohort 1); stable disease (Cohort 2), or partial or complete response (Cohort 3). Atezolizumab was administered 1200mg IV every three weeks. The primary endpoint was best overall response by RECIST v1.1. Within each cohort, a stopping rule for futility was implemented using Simon’s optimal two-stage design if none of the first eleven evaluable patients within a cohort had an objective response.

Results:: Twenty-eight patients were enrolled and treated with atezolizumab, 24 of whom had subsequent radiographic imaging. In Cohort 1, two of 17 patients achieved a PR (11.8%; 95% CI 1.5–36.4%) lasting 9 months and 3 months. While Cohort 1 met criteria to proceed to the second stage of the two-stage design, this and other cohorts closed prematurely due to slow accrual. One additional patient had a PR in Cohort 3 lasting 21 months. Grade ≥3 TRAEs occurred in 14.3% of patients.

Conclusion:: Durable responses were noted in patients with PD-1 experienced advanced NSCLC. A response rate of about 10% suggests a benchmark against which novel immunotherapy combinations should be measured in immunotherapy experienced NSCLC.