Durvalumab plus chemotherapy prior to chemoradiotherapy and followed by durvalumab as consolidation for patients with limited-stage small cell lung cancer (CONCUR study).

Abstract

TPS8139 Background: The ADRIATIC study demonstrated that durvalumab consolidation therapy following concurrent chemoradiotherapy (CRT) significantly improved both progression free survival (PFS) and overall survival (OS) in patients with inoperable limited-stage small-cell lung cancer (LS-SCLC), establishing the standard of care for this population. Building on emerging immune checkpoint inhibitor (ICI) strategies (pre-CRT induction, post-CRT consolidation or concurrent ICI-CRT), CONCUR study innovatively introduces durvalumab plus chemotherapy as induction to synergize early immune priming with cytotoxic effects, aiming to enhance responses during subsequent CRT while preserving safety, with potential to reshape the treatment landscape for LS-SCLC. Methods: Approximately 100 eligible patients (aged ≥ 18 years) with histologically or cytologically confirmed LS-SCLC, ECOG 0-1, at least one measurable lesion (RECIST 1.1), having received no prior thoracic radiotherapy or chemotherapy will be enrolled in this multi-center, phase II study. Patients will receive durvalumab (1500mg day[D] 1) combined with cisplatin (75 mg/m² D1 or 25 mg/m² D1-3) or carboplatin (AUC 5-6 D1 or AUC 2.5-3 D1 and D8) and etoposide (100 mg/m² D1-3) every 3 weeks for 2 cycles as induction therapy, followed by concurrent or sequential CRT. Thoracic radiotherapy will be delivered as 60 ± 6 Gy (1.8-2 Gy/day) or 45 ± 1.5 Gy (1.5Gy twice daily), with optional prophylactic cranial irradiation per clinical indication and local clinical practice. Patients showing at least stable disease after the definitive CRT will continue durvalumab (1500 mg every 4 weeks) until disease progression, unacceptable toxicities, or for up to 24 months (whichever occurs first). The primary endpoint is PFS by investigator per RECIST 1.1. Secondary endpoints include OS, objective response rate, duration of response, and safety. The primary analysis on PFS will be performed at approximately 60% data maturity. Assuming the median PFS is 16 months (defined from first dose of treatment), with an enrollment period of 12 months and drop-out rate of 7%, 100 patients and 60% PFS maturity will provide a precision of ± 4.8 months with 95% CI (11.6m, 21.1m) estimated by Kaplan-Meier method using Brookmeyer and Crowley method. Enrollment is ongoing. Clinical trial information: NCT07055581 .