Abstract
Immunotherapy combined with chemotherapy regimen has been shown to be effective in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, due to the small number of patients, its efficacy remains controversial in Asian populations, particularly in mainland China. Here a randomized, double-blind phase 3 trial evaluated the efficacy and safety of finotonlimab (SCT-I10A), a programmed cell death 1 (PD-1) monoclonal antibody, combined with cisplatin plus 5-fluorouracil (C5F) for the first-line treatment of R/M HNSCC. Eligible patients (n = 370) were randomly 2:1 assigned to receive finotonlimab plus C5F (n = 247) or placebo plus C5F (n = 123). The primary endpoint was overall survival (OS). In the finotonlimab plus C5F group, OS was 14.1 months (95% confidence interval (CI) 11.1–16.4), compared with 10.5 months (95% CI 8.1–11.8) in the placebo plus C5F group. The hazard ratio was 0.73 (95% CI 0.57–0.95, P = 0.0165), meeting the predefined superiority criteria for the primary endpoint. Finotonlimab plus C5F showed significant OS superiority compared with C5F alone and acceptable safety profile with R/M HNSCC, supporting its use as a first-line treatment option for R/M HNSCC. These results validate the efficacy and safety of the combination of finotonlimab and C5F in Asian patients with R/M HNSCC. ClinicalTrials.gov identifier: NCT04146402.
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Data availability
The supporting data for most figures and tables can be found directly within them, while the subgroup analysis data are available in Supplementary Information. Patient-related information cannot be disclosed due to confidentiality agreements. The trial protocol and statistical analysis plan (SAP) will be made available in Supplementary Information. For inquiries regarding access to clinical study documents, please direct your email to the corresponding author with detailed proposals. Requests will be promptly reviewed by the primary investigator and the sponsor to ascertain whether they are subject to any confidentiality obligations. We aim to respond to all requests within 8 weeks. Source data are provided with this paper.
Code availability
Analyses were carried out using commercially available software (SAS version 9.4, SAS Institute Inc.) in accordance with SAP guidelines.
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Acknowledgements
We express our appreciation for the exceptional dedication and contributions of N. Zhang and X. Liu for the operation and management and D. Liu and J. Yi for the statistical analyses. Medical writing of this manuscript was provided by C. Liu and Y. Chen. We thank H. Zhu (National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College) for editorial assistance in the writing of this manuscript. This study was sponsored by Sinocelltech Ltd., Beijing, China, who contributed to trial design, data analyses and preparation of the manuscript. This study was funded by the National Key Research and Development Program of China (2023YFC3042100) and the National Science and Technology Major Projects for Key New Drug Development of China (2019ZX09732-001 and 2017ZX09304015). The funding award has been granted to the study itself and not to any individual author or researcher.
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Y. Shi was the principal investigator, contributing to trial design, supervision, coordination, patient enrollment, patient management, manuscript writing and revising. W. Guo, W.W., Yunteng Wu, M.F., X.H., P.H., Q.Z., P.D., X.Z., H.P., C.H., X.C., Shurong Zhang, Z.C., X.L., Y.D., S.Q., S.J., Songnan Zhang, L.G., Y. Sun, L.W., Y.L., H.W., G.L., Z.F., J.S., H.J., Y.B., J. Cui., Y.Z., W.C., X.J., L.Z., Q.C., D.X., Yunong Wu, J. Cao., R.W., G.H. and L.P. were investigators in this clinical trial, and contributed to patient enrollment and patient management. L.X. contributed to the experimental design, overall management and communication. W. Gai, Y. Wang and Y. Su contributed to the trial design, medical monitoring and supervision of the trial. All authors had access to all data in the trial and were ultimately responsible for the decision to submit the manuscript for publication. The authors were responsible for the accuracy and completeness of the data and the fidelity of the trial to the protocol. All authors read and approved the final version of the manuscript for publication.
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L.X., W. Gai, Y. Wang and Y. Su are employees of Sinocelltech Ltd., Beijing, China. L.X. and W.G. hold potential stock option interests in the company. The other authors, who are investigators involved in this study, declare no competing interests.
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Nature Medicine thanks Alain Algazi, Charlotte Zuur and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Ulrike Harjes, in collaboration with the Nature Medicine team.
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Supplementary Table 1, Protocol and Statistical analysis plan.
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Shi, Y., Guo, W., Wang, W. et al. Finotonlimab with chemotherapy in recurrent or metastatic head and neck cancer: a randomized phase 3 trial. Nat Med 30, 2568–2575 (2024). https://doi.org/10.1038/s41591-024-03110-7
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DOI: https://doi.org/10.1038/s41591-024-03110-7
