3697 - Tislelizumab Combined with Chemotherapy Followed by Consolidative Thoracic Radiotherapy as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study

Background: Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with poor prognosis. First-line immune checkpoint inhibitor (ICI) plus chemotherapy therapy has improved median overall survival (mOS) to 12-17 months. Radiotherapy can enhance the release of tumor-associated antigens and exert a synergistic effect to boost immunotherapy. Recent studies have demonstrated that immunotherapy combined with consolidative thoracic radiotherapy (TRT) is associated with improved control of thoracic lesions and favorable survival outcomes. A phase II prospective trial investigated adebrelimab (a PD-L1 antibody) plus first-line chemotherapy followed by TRT combined with adebrelimab in ES-SCLC.The study demonstrated promising efficacy (mOS 21.4 months and median progression-free survival [mPFS] 10.1 months, respectively) and safety in ES-SCLC. However, data supporting PD-1 inhibitors in this sequential paradigm remain limited.

Purpose/Objective(s): Our study (Clinical Trial Registration Number: NCT07425795.) aims to evaluate the efficacy and safety of the PD-1 inhibitor tislelizumab combined with chemotherapy followed by consolidative TRT as first-line treatment for ES-SCLC.

Materials/Methods: This is a prospective, single-arm, phase II trial.The key inclusion criteria include: age 18 to 75 years; histologically or cytologically confirmed ES-SCLC per the Veterans Administration Lung Cancer Group (VALG) staging system; no prior systemic therapy for ES-SCLC; measurable lesions assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1); Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; expected survival of at least 3 months; and adequate hematologic and end-organ function. A total of 36 treatment-naive ES-SCLC patients meeting the eligibility criteria are planned to be enrolled. All patients will receive 4 to 6 cycles of induction therapy with tislelizumab combined with etoposide plus platinum-based chemotherapy. Post-induction efficacy is assessed per RECIST v1.1. Patients achieving complete response or partial response proceed to consolidative TRT (=30 Gy in 10 fractions, 45 Gy in 30 fractions [1.5 Gy BID], or =50 Gy in 25 fractions) combined with tislelizumab, initiated within 6-7 weeks of induction completion. Maintenance therapy with tislelizumab continues until disease progression, unacceptable toxicity, or consent withdrawal, for a maximum of 2 years. The primary endpoint is PFS. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DoR), OS, and safety. Exploratory endpoints include the dynamic profile of peripheral blood genomic alterations. Efficacy is assessed by investigators per RECIST v1.1.

Results: The trial is currently ongoing.

Conclusion: The trial is currently ongoing.