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Clinical Studies

A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer

British Journal of Cancer volume 130, pages 450–456 (2024)Cite this article

Subjects

Abstract

Background

Cadonilimab is a bispecific antibody that simultaneously targets programmed cell death receptor-1 and cytotoxic T lymphocyte-associated antigen-4. This study aimed to assess the safety and efficacy of cadonilimab plus anlotinib for the first-line treatment of advanced non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK/ROS1 mutations.

Methods

Patients received cadonilimab 15 mg/kg and 10 mg/kg every three weeks (Q3W) plus anlotinib at doses of 10 or 12 mg once daily for two weeks on a one-week-off schedule. The primary endpoints included safety and objective response rate (ORR).

Results

Sixty-nine treatment-naïve patients received cadonilimab 15 mg/kg Q3W combination (n = 49) and 10 mg/kg Q3W combination (n = 20). Treatment-related adverse events (TRAEs) were reported in 48 (98.0%) and 19 (95.0%) patients, with grade ≥3 TRAEs occurring in 29 (59.2%) and five (25.0%) patients, respectively. TRAEs leading to cadonilimab discontinuation occurred in eight (16.3%) and one (5.0%) patients in the cadonilimab 15 mg/kg Q3W and 10 mg/kg Q3W dosing groups. The confirmed ORRs were 51.0% (25/49) and 60.0% (12/20) accordingly.

Conclusions

Cadonilimab 10 mg/kg Q3W plus anlotinib showed manageable safety and promising efficacy as a first-line chemo-free treatment for advanced NSCLC.

ClinicalTrials.gov identifier

NCT04646330.

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Fig. 1: Trial profile.
Fig. 2: Antitumour activity and treatment duration.
Fig. 3: Progression-free survival (PFS) in patients treated with cadonilimab 15 mg/kg and 10 mg/kg every 3 weeks (Q3W).

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Data availability

All data related to the study are included in the article or the supplementary materials. Individual participant data will not be available.

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Acknowledgements

This work was funded by Akeso Biopharma Inc. We thank all patients and their families who participated in this study, along with all investigators and site personnel. We would like to thank Springer Nature (www.springernature.com) for English language editing.

Funding

This work was supported by Akeso Biopharma, Inc. and The Science and Technology Innovation Program of Hunan Province (2023SK4024).

Author information

Author notes

  1. These authors contributed equally: Bolin Chen, Wenxiu Yao, Xingya Li, Gen Lin.

Authors and Affiliations

  1. The Second Department of Thoracic Medicine, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China

    Bolin Chen, Liyu Liu, Li Xu, Yan Xu, Fang Xu, Yi Kong, Xingxiang Pu, Kang Li, Qianzhi Wang, Jia Li & Lin Wu

  2. Department of Oncology, Sichuan Cancer Hospital, Chengdu, China

    Wenxiu Yao

  3. The Second Ward, Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

    Xingya Li

  4. Department of Thoracic Oncology, Fujian Cancer Hospital, Fuzhou, China

    Gen Lin

  5. Department of Thoracic Oncology, Tongji Hospital Affiliated to Tongji Medical College of HUST, Wuhan, China

    Qian Chu

  6. Department of Oncology, Chenzhou First People’s Hospital, Chenzhou, China

    Hailong Liu

  7. Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Yingying Du

  8. Department of Medical Oncology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China

    Jie Lin

  9. Department of Oncology, Hunan Provincial People’s Hospital /The First Affiliated Hospital of Hunan Normal University, Changsha, China

    Huaxin Duan

  10. The Second Department of Respiratory Medicine, Henan Cancer Hospital, Zhengzhou, China

    Huijuan Wang

  11. Department of Oncology, The First People’s Hospital of Changde City, Changde, China

    Zemin Xiao

  12. Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

    Hong Sun

  13. Akeso Biopharma, Inc, Zhongshan, China

    Baiyong Li & Yu Xia

Authors
  1. Bolin Chen
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Contributions

BC, WY, XL, and GL: Formal analysis, Investigation, Resources, Data Curation, Writing - Original Draft, Writing - Review & Editing. QC, HL, YD, JL, HD, HW, ZX, HS, LL, LX, YX, FX, YK, XP, KL, QW, and JL: Investigation, Resources, Data curation, Writing - Review & Editing. BL, and YX: Conceptualization, Methodology, Resources, Writing - Review & Editing, Supervision, Project administration. LW: Conceptualization, Methodology, Investigation, Resources, Data curation, Writing - Review & Editing, Supervision, Project administration, Funding acquisition.

Corresponding author

Correspondence to Lin Wu.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the ethics committee of Hunan Cancer Hospital (approval number: 2018L02552) and the institutional review boards or independent ethics committees of all other participating centers. The trial was conducted in accordance with the International Conference on Good Clinical Practice Standards and the Declaration of Helsinki. All patients provided written informed consent before study participation.

Competing interests

LW reported personal fees from AstraZeneca, Roche, Bristol-Myers Squibb, MSD, Pfizer, Lilly, Johnson and Johnson, GSK, Bayer, Sanofi, Boehringer Ingelheim, Merck, Innovent, and Hengrui outside the submitted work. No disclosures were reported by the other authors.

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Chen, B., Yao, W., Li, X. et al. A phase Ib/II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) plus anlotinib as first-line treatment in patients with advanced non-small cell lung cancer. Br J Cancer 130, 450–456 (2024). https://doi.org/10.1038/s41416-023-02519-0

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