198P Adebrelimab with concurrent chemoradiation (cCRT) for limited-stage small cell lung cancer (LS-SCLC): Safety run-in results of a phase III trial

cCRT is the standard of care in LS-SCLC, but LS-SCLC still represents a significant unmet medical need with a median survival of 25 to 30 mo. Addition of the anti-PD-L1 antibody adebrelimab to carboplatin and etoposide has demonstrated survival benefits in extensive-stage SCLC in the phase 3 CAPSTONE-1 trial. This ongoing, 2-stage, phase 3 study aims to evaluate cCRT with adebrelimab in LS-SCLC. In the safety run-in stage, patients with pathologically confirmed, unresectable LS-SCLC were enrolled. Treatment consisted of four 3-week cycles of adebrelimab (20 mg/kg, iv, d1, Q3W) plus carboplatin (AUC 5, iv, d1, Q3W) and etoposide (100 mg/m2, iv, d1, 2, 3, Q3W), with thoracic radiotherapy started on cycle 3 (60 Gy/2 Gy, QD, 6 weeks). Following cCRT, patients received maintenance adebrelimab (20 mg/kg, iv, Q3W) until disease progression or unacceptable toxicities. The primary endpoint was safety. In the safety run-in stage, 28 patients were enrolled and all received adebrelimab with cCRT. As of Oct. 31, 2023, median follow-up was 29.4 mo (range 6.5-33.3). Grade ≥3 TRAEs occurred in 27 (96.4%) patients; all events with an incidence of ≥10% were hematological toxicities. Four (14.3%) patients had treatment-related pneumonitis and one (3.6%) had treatment-related immune-mediated lung disease (all grade 2). TRAEs led to treatment discontinuation in one (3.6%; infusion-related reactions) patient. There were no deaths due to TRAEs. Confirmed ORR was 92.9% (26/28; 95% CI 76.5-99.1) and DCR was 100% (28/28; 95% CI 87.7-100). Among responders, median DoR was 20.1 mo (95% CI 7.7-not reached NR; 11/26 responses ongoing). Median PFS was 17.9 mo (95% CI 8.8-NR). Median OS was NR and the OS rate at 2 years was 64.3% (95% CI 43.8-78.9). In the safety run-in stage, adebrelimab with cCRT showed acceptable tolerability and favorable efficacy outcomes in LS-SCLC. The randomized, double-blind, placebo-controlled stage of the trial is ongoing to further assess the regimen.