Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer

BACKGROUND: Programmed death-ligand 1 (PD-L1) protein is expressed in various cancers, including small-cell lung cancer (SCLC). Atezolizumab inhibits PD-L1 signaling, thus restoring tumor-specific T-cell immunity. Here, we report results from the first-in-human phase 1 PCD4989g study (NCT01375842) of atezolizumab, in a cohort of patients with relapsed/refractory SCLC. PATIENTS AND METHODS: Eligible patients with incurable or metastatic SCLC, which was advanced or recurrent since the last antitumor therapy, received atezolizumab 15 mg/kg or 1200 mg intravenously every 3 weeks for 16 cycles or until loss of clinical benefit. The primary endpoint was safety. Efficacy and biomarkers of antitumor activity were also assessed. RESULTS: Seventeen patients were enrolled. Any-grade and grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 (64.7%) and 5 (29.4%) patients, respectively. The most common any-grade TRAE was fatigue (4 patients 23.5%). Partial response to atezolizumab was achieved in 1 patient (5.9%) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), and 3 (17.6%) per immune-related response criteria (irRC). Durations of response were 2.8 to > 45.7 months. Median investigator-assessed progression-free survival (PFS) per RECIST v1.1 and irRC was 1.5 (95% confidence interval CI, 1.2-2.7) and 2.9 (95% CI, 1.2-6.1) months, respectively. Median overall survival (OS) was 5.9 months (95% CI, 4.3-12.6). Patients with high (≥ median expression) T-effector gene signature and PD-L1 mRNA expression appeared to show a trend toward improved PFS (per irRC) and OS. CONCLUSION: Atezolizumab was generally well tolerated and exhibited antitumor activity in a small cohort of patients with relapsed/refractory SCLC.