Sintilimab plus concurrent chemoradiotherapy for treatment of locally advanced small cell lung cancer (SINCE-01): a phase II clinical trial

Patients diagnosed with limited-stage small cell lung cancer (LS-SCLC) face dismal long-term outcomes, as relapse occurs frequently even after standard concurrent chemoradiotherapy. Integrating immune checkpoint blockade into chemoradiotherapy regimens may enhance sustained disease control, yet prospective evidence for this strategy in LS-SCLC remains sparse. In this single-arm phase II study, we investigated sintilimab in combination with concurrent chemoradiotherapy (CCRT) among LS-SCLC patients who had favorable functional status. Twenty-two histologically verified LS-SCLC patients were treated with four 3-weekly cycles of chemotherapy alongside sintilimab, with concurrent thoracic radiation (45 Gy delivered in 30 fractions). The primary endpoint was progression-free survival (PFS). After a median follow-up of 44.7 months, the median PFS reached 29.6 months, with 12- and 24-month PFS rates of 72.7% and 54.5%, respectively. Median overall survival (OS) stood at 40.6 months, and the corresponding 12- and 24-month OS rates were 95.5% and 72.7%, respectively. An objective response rate (ORR) of 95.5% was observed. Most grade 3–4 adverse events were hematologic in nature, particularly neutropenia and thrombocytopenia. Three patients developed pneumonitis, one of whom had grade 2 or higher. No deaths attributable to treatment occurred. Elevated human leukocyte antigen class I (HLA-I+) tumor cell expression correlated with longer PFS, suggesting potential value as a predictive biomarker. These findings suggest that concurrent administration of sintilimab with CCRT demonstrates encouraging antitumor efficacy and a manageable safety profile in LS-SCLC. (Trial registration number: ChiCTR2100043184).