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Efficacy and safety of geptanolimab (GB226) for relapsed/refractory primary mediastinal large B-cell lymphoma: an open-label phase II study (Gxplore-003)

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Abstract

Background

This study aimed to assess the efficacy and safety of geptanolimab (GB226), a fully humanized, recombinant anti-programmed cell death-1 monoclonal antibody, in Chinese patients with refractory or relapsed (r/r) primary mediastinal large B-cell lymphoma (PMBCL).

Methods

This was a multicenter, open-label, single-arm phase II study (Gxplore-003), conducted at 43 hospitals in China (NCT03639181). Patients received geptanolimab intravenously at a dose of 3 mg/kg every 2 weeks until documented confirmed disease progression, intolerable toxicity, or any other cessation criteria was met. The primary endpoint was objective response rate (ORR) in the full analysis set assessed by the independent review committee (IRC) according to the Lugano Classification 2014.

Results

This study was prematurely terminated due to the slow rate of patient accrual. Between Oct 15th, 2018 and Oct 7th, 2020, 25 patients were enrolled and treated. By the data cutoff date on Dec 23rd, 2020, the IRC-assessed ORR was 68.0% (17/25; 95% confidence interval [CI] 46.5–85.1%), with the complete response rate of 24%. The disease control rate was 88% (22/25; 95%CI 68.8–97.5%). Median duration of response was not reached (NR) (95%CI, 5.62 months to NR), with 79.5% of patients having response durations of more than 12 months. Median progression-free survival was NR (95%CI, 6.83 months to NR). Treatment-related adverse events (TRAEs) were reported in 20 of 25 (80.0%) patients, and grade 3 or higher TRAEs occurred in 11 of 25 (44%) patients. No treatment-related deaths occurred. The immune-related adverse events (irAEs) of any grade were observed in 6 (24.0%) patients, and no grade 4 or grade 5 irAEs were reported.

Conclusion

Geptanolimab (GB226) demonstrated promising efficacy and a manageable safety profile in Chinese patients with r/r PMBCL.

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Data availability

Data generated and analyzed in this study are on file with Genor Biopharma Co., Ltd., Shanghai, China and are not publicly available according to the company.

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Acknowledgements

We thank for all the patients and their families, all the investigators and study teams that contributed to this study. The authors would also like to thank Dr. Haizhu Chen (National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, China) for providing medical writing assistance with this article, funded by Genor Biopharma Co., Ltd., Shanghai, China.

Funding

This study was funded by Genor Biopharma Co., Ltd., Shanghai, China and partly supported by China National Major Project for New Drug Innovation (2017ZX09304015).

Author information

Authors and Affiliations

  1. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China

    Yuankai Shi

  2. Department of Hematology, Gansu Provincial Cancer Hospital, Lanzhou, China

    Jie Cui

  3. Department of Lymphoma and Hematology, Hunan Cancer Hospital, Changsha, China

    Hui Zhou

  4. Department of Hematology, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China

    Xiaohong Zhang

  5. Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China

    Liqun Zou

  6. Department of Hematology, Fudan University Shanghai Cancer Center, Shanghai, China

    Junning Cao

  7. Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

    Yuhuan Gao

  8. Department of Medical Oncology, The Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China

    Chuan Jin

  9. Department of Medical Oncology, Liaoning Cancer Hospital and Institute, Shenyang, China

    Xiaoling Li

  10. Department of Hematology, Beijing Hospital, Beijing, China

    Hui Liu

  11. Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China

    Zhigang Peng

  12. Department of Hematology, West China Hospital, Sichuan University, Chengdu, China

    Liping Xie

  13. Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Huilai Zhang

  14. Department of Hematology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, China

    Weihua Zhang

  15. Department of Oncology, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, China

    Hongyu Zhang

  16. Department of Hematology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

    Liye Zhong

  17. Department of Hematology, The 960th Hospital of the PLA Joint Logistics Support Force, Tai’an, China

    Fang Zhou

  18. Department of Medical Science, Genor Biopharma Co., Ltd., Shanghai, China

    Genny Guo & Wenduo He

Authors
  1. Yuankai Shi
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  2. Jie Cui
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Contributions

YKS was the leading principal investigator, and contributed to the conceptualization and design of this study, study supervision, data acquisition and interpretation, manuscript writing and revision. YKS, JC, HZ, XHZ, LQZ, JNC, YHG, CJ, XLL, HL, ZGP, LPX, HLZ, WHZ, HYZ, LYZ and FZ contributed to patient recruitment and data acquisition. GG and WDH contributed to data collection, data analysis and data interpretation. All authors had full access to the data in this study, reviewed and approved the final version for submission.

Corresponding author

Correspondence to Yuankai Shi.

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Conflict of interest

Genny Guo and Wenduo He are employees of Genor Biopharma Co., Ltd., Shanghai, China. All other authors declare no competing interests.

Ethics approval

This study was conducted in accordance with the Declaration of Helsinki and International Council for Harmonisation guidelines for Good Clinical Practice. The study protocol, amendments, and patient informed consent were approved by the independent ethics committee at each participating hospital.

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Written informed consent was obtained from all patients before screening.

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Shi, Y., Cui, J., Zhou, H. et al. Efficacy and safety of geptanolimab (GB226) for relapsed/refractory primary mediastinal large B-cell lymphoma: an open-label phase II study (Gxplore-003). Cancer Immunol Immunother 72, 2991–3002 (2023). https://doi.org/10.1007/s00262-023-03467-7

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