Danburstotug, an anti-PD-L1 antibody, in relapsed/refractory extra-nodal natural killer/T-cell lymphoma: The phase 2 DISTINKT study.

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.