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571 Penpulimab for relapsed/refractory (R/R) classical hodgkin's lymphoma (cHL): Extended follow-up of the multicenter, single-arm, phase 2 study
  1. Yuqin Song1,
  2. Keshu Zhou2,
  3. Chuan Jin3,
  4. Zhengzi Qian4,
  5. Ming Hou5,
  6. Lei Fan6,
  7. Fei Li7,
  8. Kaiyang Ding8,
  9. Hui Zhou9,
  10. Xiaoling Li10,
  11. Bing Chen11,
  12. Xiuhua Sun12,
  13. Xianmin Song13,
  14. Ming Jiang14,
  15. Qingyuan Zhang15,
  16. Lihong Liu16,
  17. Guohua Yu17,
  18. Yu Hu18,
  19. Zheng Zhao19,
  20. Ligen Liu20,
  21. Hongwei Xue21,
  22. Jun Luo22,
  23. Bai He23,
  24. Zhifang Yao24,
  25. Fenghua Xu24,
  26. Min Zhao24,
  27. Baiyong Li24,
  28. Yu Xia24 and
  29. Jun Zhu1
  1. 1Peking University Cancer Hospital & Institute, Beijing, China
  2. 2The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China
  3. 3Cancer Hospital Affiliated to Guangzhou Medical University, Guangzhou, China
  4. 4Tianjin 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 Rese, Tianjin, China
  5. 5Qilu Hospital, Shandong University, Jinan, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Jinan, China
  6. 6The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
  7. 7The First Affiliated Hospital of Nanchang University, Nanchang, China
  8. 8The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  9. 9Tumor Hospital of Xiangya School of Medicine of Central South University, Lymphoma & Hematology Department, China
  10. 10Liaoning Cancer Hospital and Institute, Shenyang, China
  11. 11Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
  12. 12Second Affiliated Hospital of Dalian Medical University, Dalian, China
  13. 13Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China
  14. 14West China Hospital, Sichuan University, Chengdu, China
  15. 15Heilongjiang Provincial Hospital, Harbin, China
  16. 16The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  17. 17Weifang People's Hospita, Weifang, China
  18. 18Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  19. 19Shaanxi Provincial Cancer Hospital, Xi'an, China
  20. 20Shanghai Tongren Hospital, Shanghai, China
  21. 21The Affiliated Hospital of Qingdao University, Qingdao, China
  22. 22The First Affiliated Hospital of Guangxi Medical University, Nanning, China
  23. 23The Third Affiliated Hospital of Suzhou University, The First People's Hospital of Changzhou, Changzhou, China
  24. 24Akeso Biopharma Co., Ltd., Zhongshan, China


Background Nearly all anti-PD-1 antibodies are of the IgG4 isotype which may possess residual crystallizable fragment (Fc) gamma receptor (FcγR) effector functions and are also associated with immune tolerance and escape due to instability of the CH3 domain and Fc-Fc interaction. Penpulimab is a novel IgG1 anti-PD-1 antibody that has a good stability and reduced host cell protein residue. Penpulimab was engineered to eliminate Fc-mediated effector function that compromises anti-tumor immune cell function. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which may contribute to slower binding off-rate. In this trial, we examined the efficacy and safety of penpulimab in patients (pts) with R/R cHL. Here we report results from up to 30 months follow-up.

Methods AK105-201 (NCT03722147) is a multicenter, single-arm, open-label study of penpulimab in R/R cHL. Adult pts (≥18 years of age) received penpulimab 200 mg once biweekly until progression or unacceptable toxicities. Eligible pts had prior autologous stem cell transplant (ASCT) or at least 2 lines of prior chemotherapy. The primary endpoint was ORR based on the Lugano 2014 criteria as assessed by an independent review committee (IRC). Key secondary endpoints included complete response (CR) rate, 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. As of the data cutoff date (Dec 31, 2021), the median follow-up was 29.5 months. Median number of treatment cycles was 26.1 (range 2–36). 85 patients meted the definition of primary efficacy population-IRC. Efficacy data is presented in (table 1). TRAEs (with unlikely related events included) occurred in 98.9% of pts (≥ G3 in 28.7% [27/94], treatment discontinuation in 6.4% [6/94]). Treatment related serious adverse event (SAEs) occurred in 12.8%. Most frequent TRAEs were hypothyroidism (33.0%), upper respiratory tract infection (26.6%), fever (24.5%), and ALT elevations (24.5%). Grade ≥3 TRAEs reported in ≥3 pts were platelet count decreased (3.2%), hyperlipemia (3.2%), rash (3.2%). In addition, 52 (55.3%) patients experienced an irAEs. The most frequent irAE was hypothyroidism (51.1%), and 4 (4.3%) patients developed grade 3 irAEs. No grade 4 or 5 irAEs were reported. No new safety signals were observed.

Conclusions Penpulimab was well tolerated, with a good safety profile in long-term use in R/R cHL pts. It demonstrated promising therapeutic activity and continued PFS and OS benefit.

Trial Registration NCT03722147

Ethics Approval The study was approved by relevant ethic committees and institutional review boards.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Abstract 571 Table 1

Efficacy data evaluated by IRC based on 2014 Lugano classification in the full analysis set (FAS; n=85)

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