Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma
Journal
Nature communications
Journal Volume
14
Journal Issue
1
Date Issued
2023-05-15
Author(s)
Lim, Darren Wan-Teck
Suteja, Lisda
Li, Constance H
Quah, Hong Sheng
Tan, Daniel Shao-Weng
Tan, Sze-Huey
Tan, Eng-Huat
Tan, Wan-Ling
Lee, Justina Nadia
Wee, Felicia Yu-Ting
Jain, Amit
Goh, Boon-Cher
Chua, Melvin L K
Ng, Quan Sing
Ang, Mei-Kim
Yeong, Joe Poh-Sheng
Iyer, N Gopalakrishna
Abstract
Single-agent checkpoint inhibitor (CPI) activity in Epstein-Barr Virus (EBV) related nasopharyngeal carcinoma (NPC) is limited. Dual CPI shows increased activity in solid cancers. In this single-arm phase II trial (NCT03097939), 40 patients with recurrent/metastatic EBV-positive NPC who failed prior chemotherapy receive nivolumab 3 mg/kg every 2 weeks and ipilimumab 1 mg/kg every 6 weeks. Primary outcome of best overall response rate (BOR) and secondary outcomes (progression-free survival [PFS], clinical benefit rate, adverse events, duration of response, time to progression, overall survival [OS]) are reported. The BOR is 38% with median PFS and OS of 5.3 and 19.5 months, respectively. This regimen is well-tolerated and treatment-related adverse events requiring discontinuation are low. Biomarker analysis shows no correlation of outcomes to PD-L1 expression or tumor mutation burden. While the BOR does not meet pre-planned estimates, patients with low plasma EBV-DNA titre (<7800 IU/ml) trend to better response and PFS. Deep immunophenotyping of pre- and on-treatment tumor biopsies demonstrate early activation of the adaptive immune response, with T-cell cytotoxicity seen in responders prior to any clinically evident response. Immune-subpopulation profiling also identifies specific PD-1 and CTLA-4 expressing CD8 subpopulations that predict for response to combined immune checkpoint blockade in NPC.
SDGs
Type
journal article