. 2022 Jul 7:12:925236.

doi: 10.3389/fonc.2022.925236. eCollection 2022.

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201)

Yuqin Song¹, Keshu Zhou², Chuan Jin³, Zhengzi Qian⁴, Ming Hou⁵, Lei Fan⁶, Fei Li⁷, Kaiyang Ding⁸, Hui Zhou⁹, Xiaoling Li¹⁰, Bing Chen¹¹, Xiuhua Sun¹², Xianmin Song¹³, Ming Jiang¹⁴, Qingyuan Zhang¹⁵, Lihong Liu¹⁶, Guohua Yu¹⁷, Yu Hu¹⁸, Zheng Zhao¹⁹, Ligen Liu²⁰, Hongwei Xue²¹, Jun Luo²², Bai He²³, Xiaoping Jin²⁴, Min Zhao²⁴, Baiyong Li²⁴, Yu Xia²⁴, Jun Zhu¹

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
² Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
³ Department of Oncology, Cancer Hospital Affiliated to Guangzhou Medical University, Guangzhou, China.
⁴ Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, the Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.
⁵ Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
⁶ Department of Hematology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
⁷ Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
⁸ Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁹ Lymphoma & Hematology Department, Tumor Hospital of Xiangya School of Medicine of Central South University, Changsha, China.
¹⁰ Department of Medical Oncology, Liaoning Cancer Hospital and Institute, Shenyang, China.
¹¹ Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
¹² Department of Medical Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
¹³ Department of Hematology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
¹⁴ Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
¹⁵ Department of Medical Oncology, Heilongjiang Provincial Hospital, Harbin, China.
¹⁶ Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
¹⁷ Clinical Oncology Department, Weifang People's Hospital, Weifang, China.
¹⁸ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁹ Third Department of Medical Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, China.
²⁰ Department of Hematology, Shanghai Tongren Hospital, Shanghai, China.
²¹ Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China.
²² Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
²³ Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, China.
²⁴ Akeso Biopharma Co., Ltd., Zhongshan, China.

PMID: 35875118
PMCID: PMC9301139
DOI: 10.3389/fonc.2022.925236

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201)

Yuqin Song et al. Front Oncol. 2022.

. 2022 Jul 7:12:925236.

doi: 10.3389/fonc.2022.925236. eCollection 2022.

Authors

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
² Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
³ Department of Oncology, Cancer Hospital Affiliated to Guangzhou Medical University, Guangzhou, China.
⁴ Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, the Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.
⁵ Department of Hematology, Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China.
⁶ Department of Hematology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China.
⁷ Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
⁸ Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
⁹ Lymphoma & Hematology Department, Tumor Hospital of Xiangya School of Medicine of Central South University, Changsha, China.
¹⁰ Department of Medical Oncology, Liaoning Cancer Hospital and Institute, Shenyang, China.
¹¹ Department of Hematology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
¹² Department of Medical Oncology, Second Affiliated Hospital of Dalian Medical University, Dalian, China.
¹³ Department of Hematology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
¹⁴ Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
¹⁵ Department of Medical Oncology, Heilongjiang Provincial Hospital, Harbin, China.
¹⁶ Department of Hematology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
¹⁷ Clinical Oncology Department, Weifang People's Hospital, Weifang, China.
¹⁸ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁹ Third Department of Medical Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, China.
²⁰ Department of Hematology, Shanghai Tongren Hospital, Shanghai, China.
²¹ Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China.
²² Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
²³ Department of Hematology, The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, China.
²⁴ Akeso Biopharma Co., Ltd., Zhongshan, China.

PMID: 35875118
PMCID: PMC9301139
DOI: 10.3389/fonc.2022.925236

Abstract

Background: Nearly all anti-PD-1 antibodies are of the IgG4 isotype, and thus possess residual FcR effector functions. Such anti-PD-1 antibodies are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. In this trial, we examined the efficacy and safety of penpulimab, a novel IgG1 anti-PD-1 antibody that does not bind to the Fc receptor, in patients with refractory or relapsed classical Hodgkin lymphoma (R/R cHL).

Methods: Adult patients (≥18 years of age) with R/R cHL received 200 mg penpulimab once biweekly until disease progression or unacceptable toxicities for a maximum of 24 months. The primary endpoint was objective response rate (ORR) based on the Independent Radiology Review Committee per Lugano 2014 criteria. Secondary endpoints included progression-free survival (PFS), overall survival (OS), treatment-related adverse events (TRAEs) and immune-related adverse events (irAEs).

Results: A total of 94 patients were enrolled. The median follow-up was 15.8 months. The ORR was 89.4% (95% CI 80.8%, 95.0%) in the full analysis set (85 patients). Forty (47.1%) patients achieved complete remission, 36 (42.4%) patients achieved partial remission. The 12-month PFS rate was 72.1% (95% CI 60.5%, 80.8%) and the 18-month OS rate was 100%. Totally 97.9% (92/94) of patients experienced at least one TRAE. The rate of grade 3 and above TRAEs was 26.6% (25/94). In addition, 51 (54.3%) patients experienced an irAE, and 4 (4.3%) patients developed grade 3 or above irAEs. No irAE-related death occurred.

Conclusions: Penpulimab was effective and safe in patients with R/R cHL.

Keywords: IgG1 anti-PD-1 antibody; classical Hodgkin lymphoma; efficacy; penpulimab; safety.

PubMed Disclaimer

Conflict of interest statement

XJ, MZ, BL and YX are employees of Akeso Biopharma Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Akeso Biopharma Co., Ltd. The funder had the following involvement with the study: sponsored this trial, and participated in the study design, data collection, statistical analysis, and provided medical writing support.

Figures

**Figure 1**
Swimmer plot of time to tumor response (months) of relapsed/refractory classical Hodgkin lymphoma patients receiving penpulimab. Responses were evaluated by the Independent Radiology Review Committee (IRRC) according to the 2014 Lugano classification. Each bar represents one patient in the full analysis set (FAS). CR, complete response; NA, not applicable; PD, progressive disease; PR, partial response; SD, stable disease.

**Figure 2**
**(A)** The Kaplan-Meier curve of progression-free survival (PFS) of the FAS. **(B)** The Kaplan-Meier curve of overall survival (OS) of the FAS.

**Figure 3**
Forest plot analysis of objective response rate (ORR) by patient subgroups.

See this image and copyright information in PMC

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Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201)

Affiliations

Penpulimab for Relapsed or Refractory Classical Hodgkin Lymphoma: A Multicenter, Single-Arm, Pivotal Phase I/II Trial (AK105-201)

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