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

Author

Listed:
  • Darren Wan-Teck Lim

    (National Cancer Centre Singapore
    Duke-NUS Medical School
    Institute of Molecular and Cell Biology, A*STAR)

  • Hsiang-Fong Kao

    (National Taiwan University Hospital
    National Taiwan University Cancer Center)

  • Lisda Suteja

    (National Cancer Centre Singapore
    Duke-NUS Medical School)

  • Constance H. Li

    (National Cancer Centre Singapore
    Duke-NUS Medical School)

  • Hong Sheng Quah

    (National Cancer Centre Singapore
    Duke-NUS Medical School)

  • Daniel Shao-Weng Tan

    (National Cancer Centre Singapore
    Duke-NUS Medical School
    Genome Institute of Singapore, A*STAR)

  • Sze-Huey Tan

    (National Cancer Centre Singapore
    Duke-NUS Medical School)

  • Eng-Huat Tan

    (National Cancer Centre Singapore)

  • Wan-Ling Tan

    (National Cancer Centre Singapore)

  • Justina Nadia Lee

    (Institute of Molecular and Cell Biology, A*STAR)

  • Felicia Yu-Ting Wee

    (Institute of Molecular and Cell Biology, A*STAR)

  • Amit Jain

    (National Cancer Centre Singapore)

  • Boon-Cher Goh

    (National University Health System)

  • Melvin L. K. Chua

    (National Cancer Centre Singapore
    Duke-NUS Medical School)

  • Bin-Chi Liao

    (National Taiwan University Hospital
    National Taiwan University Cancer Center)

  • Quan Sing Ng

    (National Cancer Centre Singapore)

  • Ruey-Long Hong

    (National Taiwan University Hospital
    National Taiwan University Cancer Center)

  • Mei-Kim Ang

    (National Cancer Centre Singapore)

  • Joe Poh-Sheng Yeong

    (Institute of Molecular and Cell Biology, A*STAR
    Singapore General Hospital)

  • N. Gopalakrishna Iyer

    (National Cancer Centre Singapore
    Duke-NUS Medical School
    Singapore General Hospital)

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 (

Suggested Citation

  • Darren Wan-Teck Lim & Hsiang-Fong Kao & Lisda Suteja & Constance H. Li & Hong Sheng Quah & Daniel Shao-Weng Tan & Sze-Huey Tan & Eng-Huat Tan & Wan-Ling Tan & Justina Nadia Lee & Felicia Yu-Ting Wee &, 2023. "Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38407-7
    DOI: 10.1038/s41467-023-38407-7
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    1. Sanjeev Mariathasan & Shannon J. Turley & Dorothee Nickles & Alessandra Castiglioni & Kobe Yuen & Yulei Wang & Edward E. Kadel III & Hartmut Koeppen & Jillian L. Astarita & Rafael Cubas & Suchit Jhunj, 2018. "TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells," Nature, Nature, vol. 554(7693), pages 544-548, February.
    2. Yang Liu & Shuai He & Xi-Liang Wang & Wan Peng & Qiu-Yan Chen & Dong-Mei Chi & Jie-Rong Chen & Bo-Wei Han & Guo-Wang Lin & Yi-Qi Li & Qian-Yu Wang & Rou-Jun Peng & Pan-Pan Wei & Xiang Guo & Bo Li & Xi, 2021. "Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. Yvonne Y Li & Grace T. Y. Chung & Vivian W. Y. Lui & Ka-Fai To & Brigette B. Y. Ma & Chit Chow & John K, S. Woo & Kevin Y. Yip & Jeongsun Seo & Edwin P. Hui & Michael K. F. Mak & Maria Rusan & Nicole , 2017. "Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
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