Feed

Thymic carcinoma is a rare, aggressive malignancy with limited treatment options. First-line platinum-based chemotherapy yields response rates below 40%, and immune checkpoint inhibitors have shown inconsistent efficacy. Ivonescimab, a programmed cell death protein 1/vascular endothelial growth factor (PD-1/VEGF) bispecific antibody, may enhance antitumor activity through dual blockade.This single-center, phase II trial enrolled patients with stage IVb, treatment-naïve thymic carcinoma. Patients received ivonescimab (20 mg/kg) plus paclitaxel (175 mg/m²) and carboplatin (area under the curve 5) every 3 weeks for four to six cycles, followed by ivonescimab maintenance. The primary endpoint was objective response rate (ORR) . Secondary endpoints included disease control rate (DCR) and safety. Biomarker analyses were exploratory.Between January 2025 and April 2026, seven patients were enrolled (median age 61 years; 71% male; 71% squamous). Five had evaluable tissue next-generation sequencing and six had transcriptomic data. After median follow-up of 6.4 months, the preliminary ORR was 85.7% (6/7; 95% CI 42.1% to 99.6%) and DCR 100%. The 6-month progression-free survival (PFS) and overall survival (OS) rates were both 100% (two and four patients at risk for PFS and OS, respectively). The only PFS event occurred at 15.7 months in a patient who discontinued treatment due to adverse events (AEs). Grade ≥3 treatment-related AEs occurred in 57.1% (mainly neutropenia, 42.9%); grade ≥3 immune-related AEs in 14.3%. No treatment-related deaths occurred. All tumors were microsatellite-stable with low mutational burden. Deep responders (≥50% reduction) showed a lower exploratory myeloid-derived suppressor cell-related gene-expression score (nominal p=0.10, exact Mann-Whitney U test). Baseline blood CD4⁺/CD8⁺ ratio was lower in deep responders and remained stable during treatment, vs an increase in others (nominal p=0.057). Tumorous CXCL1 expression showed an exploratory positive correlation with the CD4⁺/CD8⁺ ratio (R=0.84, nominal p=0.035, n=6).First-line ivonescimab plus paclitaxel-carboplatin showed promising preliminary antitumor activity and manageable safety in advanced thymic carcinoma. The peripheral blood CD4⁺/CD8⁺ ratio showed an exploratory association with depth of response and warrants prospective evaluation in the complete cohort and independent validation.Trial registration numberChiCTR2400094398.