Phase II randomized study of maintenance atezolizumab (A) versus atezolizumab + talazoparib (AT) in patients with SLFN11 positive extensive stage small cell lung cancer. S1929.

Purpose: To evaluate whether the addition of a poly (ADP-ribose) polymerase inhibitor (PARPi) talazoparib to maintenance immune checkpoint inhibitor (ICI) atezolizumab following frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive stage small cell lung cancer (ES-SCLC).

Methods: Patients with newly diagnosed SLFN11 expressing (H-score ≥ 1, evaluated centrally) ES-SCLC were randomized to maintenance atezolizumab (A) versus atezolizumab plus talazoparib (AT) following frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a 1-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate (ORR), overall survival (OS), and toxicity. Target sample size was 84 eligible patients.

Results: From June 15, 2020 to December 15, 2022, 106 eligible patients were randomized (54 to AT and 52 to A). PFS was improved with AT versus A (hazard ratio [HR], 0.66; 80% confidence interval [CI]: 0.50-0.86; 1-sided P = 0.019) with a median PFS of 2.9 and 2.4 months; OS was not different between groups (HR, 0.98; 80% CI: 0.71-1.36; 1-sided P = 0.47). Grade ≥ 3 non-hematologic treatment-related adverse events (TRAEs) occurred in 17% of patients with AT and 14% of patients with A. Grade ≥ 3 hematological TRAEs were more common in AT (50%) than in A (4%) (P < 0.001).

Conclusion: Maintenance AT improved PFS in patients with SLFN11-positive ES-SCLC that did not progress following initial chemo-immunotherapy. Hematologic toxicity, primarily grade 3 anemia, was increased with AT, as expected. Prospective biomarker-selection was demonstrated, paving the way for future evaluation of novel therapies in molecularly defined SCLC populations.