First-line camrelizumab plus chemotherapy followed by camrelizumab-apatinib maintenance for ES-SCLC: a single-arm phase II study.

BACKGROUND: Immune-antiangiogenic combinations have shown promising signals of activity in ES-SCLC, but the optimal timing of anti-angiogenic therapy and biomarkers associated with benefit remain undefined. This study evaluated the efficacy and safety of combining apatinib with camrelizumab during maintenance and explored immune-molecular biomarkers of benefit. METHODS: In this single-arm phase II trial, apatinib plus camrelizumab as maintenance therapy following induction therapy with camrelizumab plus platinum-etoposide chemotherapy was administered to treatment-naïve ES-SCLC patients (ACES). The primary endpoint was 6-month progression-free survival (PFS) rate; secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), PFS, and safety. Multiplex immunofluorescence (mIF) and RNA sequencing were performed as exploratory immune-molecular analyses. RESULTS: Between March 2021 and July 2024, 41 patients were enrolled. At a median follow-up of 31.0 months, the 6-month PFS rate was 71.1% (95% CI: 53.9-82.9), with median PFS and OS of 8.7 months (95% CI: 6.9-10.6) and 17.2 months (95% CI: 14.5-19.9), respectively. ORR was 82.9% and DCR was 92.7%. Grade ≥ 3 treatment-related adverse events occurred in 22.0% of patients, with no treatment-related deaths. MIF revealed that durable clinical benefit was associated with a "high-CD8+/low-M2" immune phenotype. Transcriptomic profiling suggested an exploratory 9-gene expression pattern associated with progression-free survival. CONCLUSIONS: Camrelizumab plus chemotherapy followed by camrelizumab-apatinib maintenance showed preliminary antitumor activity with manageable safety in patients with ES-SCLC. Exploratory immune-molecular profiling suggested a putative "high-CD8+/low-M2" immune phenotype and a 9-gene expression pattern associated with clinical benefit.