Consolidation thoracic radiotherapy following quadruple induction with benmelstobart, anlotinib, and chemotherapy for extensive-stage small cell lung cancer: rationale and protocol of a phase II study

Background: Extensive-stage small cell lung cancer (ES-SCLC) remains a highly aggressive malignancy with limited survival outcomes. While first-line immune checkpoint inhibitors combined with platinum-based chemotherapy have improved survival, the benefit is modest. Emerging evidence supports the integration of anti-angiogenic therapy and thoracic radiotherapy (TRT) to enhance systemic and local control. However, a comprehensive multimodal regimen combining chemotherapy, immunotherapy, anti-angiogenic therapy, and TRT has not been systematically evaluated. This study aims to assess the safety, feasibility, and preliminary efficacy of a multimodal treatment strategy involving induction with benmelstobart [an anti-programmed death-ligand 1 (PD-L1) antibody], platinum-etoposide chemotherapy, and anlotinib, followed by consolidation with benmelstobart, anlotinib, and sequential TRT in patients with untreated ES-SCLC.

Methods: This is a prospective, single-center, single-arm, phase II, open-label trial conducted at Tianjin Medical University Cancer Institute & Hospital. Twenty-five patients with histologically confirmed, treatment-naive ES-SCLC and measurable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 will be enrolled. The regimen consists of—induction phase: 4 cycles of benmelstobart 
(1,200 mg IV q21d), carboplatin (area under the curve 5) or cisplatin (75–80 mg/m²) on day 1, etoposide (100 mg/m² IV days 1–3), and oral anlotinib (12 mg once daily, 2 weeks on/1 week off); consolidation phase: 2 cycles of benmelstobart, anlotinib, and TRT (25 Gy in 5 daily fractions of 5 Gy each, administered only during the first consolidation cycle); maintenance phase: benmelstobart plus anlotinib until progression, unacceptable toxicity, or clinical deterioration. The co-primary endpoints are progression-free survival (PFS) and incidence of grade ≥3 treatment-related adverse events (TRAEs). Secondary endpoints include objective response rate and overall survival. Safety will be evaluated in all treated patients.

Discussion: This trial will provide critical preliminary evidence on the safety, feasibility, and efficacy of integrating short-course TRT into a quadruple chemo-immuno-antiangiogenic backbone for ES-SCLC. The results are expected to inform the design of future multicenter, randomized phase III trials and potentially establish a novel multimodal paradigm for first-line management.

Trial Registration: ClinicalTrials.gov identifier: NCT07358676. Protocol version: version 1.0, April 03, 2025