Phase II Randomized Study of Maintenance Atezolizumab Versus Atezolizumab Plus Talazoparib in Patients With SLFN11 Positive Extensive-Stage SCLC: S1929.

OBJECTIVE: To evaluate whether the addition of a poly (adenosine diphosphate-ribose) polymerase inhibitor talazoparib to maintenance immune checkpoint inhibitor atezolizumab after frontline chemoimmunotherapy improved outcomes in patients with Schlafen 11 (SLFN11)-positive extensive-stage SCLC (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) after frontline chemotherapy plus atezolizumab. The primary objective was to compare progression-free survival (PFS) using a one-sided 10% level stratified log-rank test. Secondary endpoints included objective response rate, overall survival, and toxicity. The 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). Progression-free survival was improved with AT versus A (hazard ratio = 0.66, 80% confidence interval: 0.50-0.86, one-sided p = 0.019) with a median PFS of 2.9 and 2.4 months; overall survival was not different between groups (hazard ratio = 0.98, 80% confidence interval: 0.71-1.36, one-sided p = 0.47). Grade 3 and higher non-hematologic treatment-related adverse events occurred in 17% of patients with AT and 14% of patients with A. Grade 3 and higher hematological treatment-related adverse events 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 after 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.