Danburstotug, an anti‐ PD ‐ L1 antibody, in relapsed/refractory extra‐nodal natural killer/T‐cell lymphoma: The phase 2 DIS

Summary

Relapsed/refractory extra‐nodal natural killer/T‐cell lymphoma (R/R ENKTL) has limited treatment options. Danburstotug, an antibody targeting programmed death‐ligand 1 (PD‐L1), was evaluated in adults with R/R ENKTL in a phase 2, open‐label study (NCT04414163). Danburstotug 20 mg/kg was administered intravenously every 2 weeks up to 52 cycles, disease progression or unacceptable toxicity. In the full analysis set ( n  = 19), objective response rate (ORR; primary end‐point) was 78.9% (95% confidence interval 54.4–94.0); complete response (CR) rate was 63.2% (38.4–83.7); 76.9% of participants maintained responses; and 90.9% of participants maintained CR for 2 years. In the intention‐to‐treat population ( n  = 23), median progression‐free survival (PFS) was 29.4 months (12.0–46.9; 2‐year PFS rate 62.1%); and median overall survival was 40.2 months (25.1–55.4; 2‐year overall survival rate 77.9%). Treatment‐emergent adverse events occurred in 91.3% of 23 participants (73/83 events were grade 1/2); grade 3 serious treatment‐related adverse events comprised liver injury and uveitis (one participant each). High PD‐L1 membrane specificity (MS) was associated with greater ORR, CR rate and PFS versus low PD‐L1 MS. In tumour immune microenvironment assessments, clinical benefit was observed across immune tolerance and immune evasion subtypes, despite lower PD‐L1 expression in immune evasion‐B. Danburstotug demonstrated robust, durable efficacy and manageable safety. PD‐L1 MS showed potential as a predictive biomarker.