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Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma

ABSTRACT: In this single arm non-randomized phase II trial, 40 patients with recurrent/metastatic EBV-positive nasopharyngeal carcinoma who failed prior chemotherapy received nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. The best overall objective response rate was 38% with a median progression-free and overall survival of 5.3 and 19.5 months, respectively. This regimen was well-tolerated and treatment-related adverse events requiring discontinuation were low. There was no correlation of response with PD-L1 expression or tumor mutation burden, however patients with low plasma circulating EBV-DNA titre (<7,800 IU/ml) showed a trend to better response and progression-free survival. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrated early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Profiling immune-subpopulations also identified a specific PD-1 and CTLA-4 expressing CD8 subpopulation that predicted for response to combined immune checkpoint blockade in nasopharyngeal carcinoma.

ORGANISM(S): Homo sapiens

PROVIDER: GSE224450 | GEO | 2023/04/13

REPOSITORIES: GEO

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