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A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma

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Abstract

Background

Immune checkpoint blockade with anti-programmed cell death 1 (PD-1) antibodies has demonstrated efficacy in multiple tumor types. Nofazinlimab is a humanized rat antibody targeting PD-1. A first-in-human study of nofazinlimab conducted in Australia found no dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) was not reached in the range of 1–10 mg/kg.

Objective

We evaluated nofazinlimab for multiple advanced malignancies in Chinese patients.

Patients and methods

This was a phase 1a/1b, open-label, multicenter, dose-escalation/expansion trial. In phase 1a, patients received an abbreviated dose escalation of nofazinlimab at 60 mg and 200 mg every 3 weeks (Q3W) to determine DLTs and the recommended phase 2 dose (RP2D). In phase 1b, patients received the RP2D (monotherapy/combination) in six arms by tumor type; DLTs were evaluated for nofazinlimab plus lenvatinib in the unresectable hepatocellular carcinoma (uHCC) arm. Safety (continuously monitored in patients who received nofazinlimab) and efficacy (patients with measurable baseline disease) were assessed.

Results

Overall, 107 patients were eligible and received nofazinlimab. In phase 1a, no DLTs were observed; the RP2D was 200mg Q3W. In phase 1b, no DLTs were observed with nofazinlimab plus lenvatinib. The safety profile was consistent with that observed in the first-in-human study (NCT03475251). In phase 1b, 21/88 (23.9%) patients achieved confirmed objective responses, 26 (29.5%) had stable disease, and 9/20 (45.0%) patients with uHCC achieved confirmed objective responses to nofazinlimab plus lenvatinib.

Conclusions

Nofazinlimab was well tolerated in Chinese patients. Preliminary efficacy was encouraging, particularly for nofazinlimab plus lenvatinib in uHCC, which is being studied in an ongoing phase 3 trial.

Clinical Trial Registration

NCT03809767; registered 18 January 2019.

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Acknowledgements

We thank the patients and their families for making this trial possible, and the investigators and clinical study teams who participated. Editorial assistance was provided by Yuanyuan Dai of CStone Pharmaceuticals Suzhou, China, and medical writing support was provided by Adam Gill, MRes, at Rude Health Consulting, funded by CStone Pharmaceuticals, Suzhou, China.

Author information

Authors and Affiliations

  1. Peking University Cancer Hospital & Institute, Beijing, China

    Jifang Gong, Ziping Wang & Lin Shen

  2. Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China

    Ye Guo

  3. Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

    Yanqiao Zhang

  4. Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Yi Ba

  5. Huashan Hospital, Fudan University, Shanghai, China

    Tong Chen

  6. The First Hospital of Jilin University, Changchun, Jilin, China

    Wei Li

  7. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

    Caicun Zhou

  8. Peking Union Medical College Hospital, Beijing, China

    Mengzhao Wang

  9. Zhejiang Cancer Hospital, Hangzhou, China

    Haiyan Yang

  10. Zhongshan Hospital, Shanghai, China

    Yuhong Zhou

  11. Henan Cancer Hospital, Zhengzhou, China

    Qiqing Cai

  12. Hunan Cancer Hospital, Changsha, China

    Gang Huang

  13. The First Affiliated Hospital of Nanchang University, Nanchang, China

    Wei Zhang

  14. CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, China

    Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu & Archie N. Tse

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  1. Jifang Gong
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  22. Lin Shen
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Corresponding author

Correspondence to Lin Shen.

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Funding

This study was funded by CStone Pharmaceuticals (Suzhou) Co., Ltd., Suzhou, China. The study sponsors collected, analyzed, and interpreted the data in conjunction with the authors, who had access to all the data.

Conflicts of interest

Lin Shen reports study funding from Astellas; grants or contracts from Beijing Xiantong Biomedical Technology, Qilu Pharmaceutical, ZaiLab Pharmaceutical (Shanghai), Beihai Kangcheng (Beijing) Medical Technology, Yaojie Ankang (Nanjing) Technology Co., Ltd., Baiji Shenzhou (Beijing) Biotechnology Co., Ltd., and Jacobio Pharmaceuticals; consulting fees from Mingji Biopharmaceuticals, Haichuang Pharmaceuticals, and Herbour BioMed; payment or honoraria for speakers bureaus from Hutchison Whampoa, Jiangsu Hengrui, ZaiLab, and CStone Pharmaceuticals; and data safety monitoring board or advisory board participation for MSD, Merck, Bristol-Meyers Squibb, Boehringer Ingelheim, Sanofi, Roche, Servier, and AstraZeneca. Rila Su, Zhongheng Cai, Zenglian Yue, Jinzhou Dou, Peiqi Li, Rachel Wu, and Archie N. Tse are employees of CStone Pharmaceuticals. Archie N. Tse and Rila Su own stock in CStone Pharmaceuticals. Jifang Gong, Ye Guo, Yanqiao Zhang, Yi Ba, Tong Chen, Wei Li, Caicun Zhou, Mengzhao Wang, Haiyan Yang, Yuhong Zhou, Qiqing Cai, Ziping Wang, Gang Huang, and Wei Zhang declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics Approval

The trial protocol was approved by an independent Ethics Committee at each study center. The trial was conducted in compliance with applicable laws in China, and in accordance with the Chinese Guidelines for Good Clinical Practice and the principles outlined in the Declaration of Helsinki.

Consent to Participate

All participants provided written, informed consent prior to participation.

Consent for Publication

Not applicable.

Availability of Data and Materials

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Author Contributions

Jifang Gong: conceptualization, data curation, formal analysis, and writing—review and editing. Ye Guo: conceptualization, data curation, formal analysis, and writing—review and editing. Yanqiao Zhang: conceptualization, data curation, formal analysis, and writing—review and editing. Yi Ba: study design, conceptualization, data curation, formal analysis, and writing—review and editing. Tong Chen: conceptualization, data curation, formal analysis, and writing—review and editing. Wei Li: conceptualization, data curation, formal analysis, and writing—review and editing. Caicun Zhou: conceptualization, data curation, formal analysis, and writing—review and editing. Mengzhao Wang: conceptualization, data curation, formal analysis, and writing—review and editing. Haiyan Yang: conceptualization, data curation, formal analysis, and writing—review and editing. Yuhong Zhou: conceptualization, data curation, formal analysis, and writing—review and editing. Qiqing Cai: conceptualization, data curation, formal analysis, and writing—review and editing. Ziping Wang: conceptualization, data curation, formal analysis, and writing—review and editing. Gang Huang: conceptualization, data curation, formal analysis, and writing—review and editing. Wei Zhang: conceptualization, data curation, formal analysis, and writing—review and editing. Rila Su: conceptualization, data curation, formal analysis, and writing—review and editing. Zhongheng Cai: conceptualization, data curation, formal analysis, and writing—review and editing. Zenglian Yue: conceptualization, data curation, formal analysis, and writing—review and editing. Jinzhou Dou: conceptualization, data curation, formal analysis, and writing—review and editing. Peiqi Li: conceptualization, data curation, formal analysis, and writing—review and editing. Rachel Wu: conceptualization, data curation, formal analysis, and writing—review and editing. Archie N. Tse: conceptualization, data curation, formal analysis, and writing—review and editing. Lin Shen: conceptualization, data curation, formal analysis, and writing—review and editing.

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Gong, J., Guo, Y., Zhang, Y. et al. A Phase 1a/1b Dose Escalation/Expansion Study of the Anti-PD-1 Monoclonal Antibody Nofazinlimab in Chinese Patients with Solid Tumors or Lymphoma. Targ Oncol 19, 723–733 (2024). https://doi.org/10.1007/s11523-024-01091-8

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