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791 A phase II study of the anti-programmed cell death-1 (PD-1) antibody penpulimab in patients with relapsed or refractory classic hodgkin lymphoma (cHL)
  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. Xiaoping Jin24,
  25. Maxwell Wang24,
  26. Baiyong Li24,
  27. Yu Xia24 and
  28. Jun Zhu25
  1. 1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
  2. 2The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Henan, 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. 5Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Qilu, China
  6. 6The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing, China
  7. 7The First Affiliated Hospital of Nanchang University, Nanchan, 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, Changsha, 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. 14Cancer Center, West China Hospital, Sichuan University, Chengdu, China
  15. 15Heilongjiang Provincial Hospital, Harbin, China
  16. 16The Fourth Hospital of Hebei Medical University, Hebei, China
  17. 17Weifang People’s Hospital, Weifang, China
  18. 18Union Hospital, Tongji Medical College, Wuhan, China
  19. 19Shanxi 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 First People’s Hospital of Changzhou, Changzhou, China
  24. 24Akeso Biopharma Inc, Potomac, Maryland, USA
  25. 25Peking University Cancer Hospital and Institute, Beijing, China


Background Penpulimab is a humanized IgG1 mAb that blocks PD-1 binding to PD-L1. Penpulimab was engineered to eliminate Fc?R binding and ADCC/ADCP completely, as compared to majority of marketed IgG4 PD-1 antibodies with ADCC/ADCP activity. ADCC/ADCP effects can induce T-cell apoptosis and clearance and then compromise anti-tumor activity. The removal of Fc?R binding eliminates Fc receptor mediated immune-cell recruitment and activation and could potentially reduce immune-related adverse reactions. Penpulimab demonstrated a slower PD-1 antigen binding off-rate than marketed PD-1 antibodies, which result in better cellular activity and higher receptor occupancy. Penpulimab also showed numerous contacts with N58 glycosylation on the BC loop of PD-1 which could be an advantage to facilitate interaction of PD-1 antibody and may contribute to slower binding off-rate. These structural differentiations offer more robust biological effect and enhance anti-tumor activity of penpulimab.

Methods AK105-201 (NCT03722147) is a multicenter, single-arm, open-label study of penpulimab in R/R cHL. All pts received penpulimab 200 mg q2w until progression or unacceptable toxicity. Eligible pts had R/R cHL after 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 CR rate, DCR, PFS, duration of response (DoR), safety, and tolerability.

Results As of 10 January, 2020, the median follow-up was 6.3 months (range, 3.5 to 17.0). The anti-tumor activity of penpulimab in the 73 pts evaluable for efficacy (defined as pts who had an opportunity to be followed for at least 16 weeks) is shown in the table 1. At data cutoff, 91.8% of responders remained ongoing and still on treatment. Treatment-related adverse events (TRAEs) occurred in 93.6% of pts (G3 in 13.8% [13/94], no G4 or G5, treatment discontinuation in 2.1% [2/94]). Treatment-related SAEs occurred in 3.2%. Most frequent TRAEs (≥15%) were fever (24.5%), hypothyroidism (21.3%), upper respiratory tract infection (18.1%), and ALT elevations (17.0%). Grade ≥3 TRAEs reported in ≥2 pts were platelet count decreased (2.1%). Immune-related AEs were reported in 42.6% of pts (G3 in 2.1%: psoriasis [n=1], IgA nephropathy [n=1]).

Abstract 791 Table 1

Anti-tumor activity of penpulimab in R/R cHL

Conclusions Penpulimab was shown to be highly active resulting in a high CR rate in pts with R/R cHL. With longer follow-up, CR rate for penpulimab in R/R cHL could be further increased. Penpulimab demonstrated notably lower rates of SAE, TRAE leading to discontinuation, and Grade Grade ≥3 immune-related AEs in pts with R/R cHL.

Trial Registration NCT03722147

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