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804 A phase II study of the anti-programmed cell death-1 (PD-1) antibody penpulimab in patients with metastatic nasopharyngeal carcinoma (NPC) who had progressed after two or more lines of chemotherapy
  1. Xiaozhong Chen1,
  2. Wei Wang2,
  3. Qingfeng Zou3,
  4. Jingao Li4,
  5. Chaosu Hu5,
  6. Chaosu Hu5,
  7. Qin Lin6,
  8. Xiaodong Zhu7,
  9. Yi Jiang8,
  10. Yan Sun9,
  11. Liangfang Shen10,
  12. Lin Wang11,
  13. Guorong Zou12,
  14. Xiaoyan Lin13,
  15. Ying Wang14,
  16. Shaojun Lin15,
  17. Minying Li16,
  18. Rui Ao17,
  19. Ruilian Xu18,
  20. Haifeng Lin19,
  21. Rensheng Wang7,
  22. Jiacheng Yang20,
  23. Weifeng Song20,
  24. Max Wang20,
  25. Baiyong Li20 and
  26. Yu Xia20
  1. 1University of Chinese Academy of Science, Zhejiang, China
  2. 2Hunan Cancer Hospital, Hunan, China
  3. 3Guangzhou Medical University, Guangzhou, China
  4. 4Jiangxi Cancer Hospital, Nanchang, China
  5. 5Fudan University, Shanghai, China
  6. 6Xiamen University, Xiamen, China
  7. 7Guangxi Medical University, Guangxi, China
  8. 8Shantou University Medical College, Shantou, China
  9. 9Beijing Cancer Hospital, Beijing, China
  10. 10Central South University, Changsha, China
  11. 11Hainan General Hospital, Haikou, China
  12. 12Cancer Institute of Panyu, Panyu, China
  13. 13Fujian Medical University Union Hospital, Fujian, China
  14. 14Chongqing Cancer Hospital, Chongqing, China
  15. 15Fujian Cancer Hospital, Fujian, China
  16. 16Zhongshan People’s Hospital, Zhongshan, China
  17. 17Sichuan Academy of Medical Sciences, Chengdu, China
  18. 18Shenzhen People’s Hospital, Shenzhen, China
  19. 19Hainan Medical University, Haikou, China
  20. 20Akeso Biopharma, Inc., Zhongshan, China


Background NPC is rare but has a distinct geographic distribution, with a predominance in Southeast Asia. Favorable results with PD-1 inhibitors in NPC provide a strong rationale to investigate penpulimab in this disease. Penpulimab was engineered to eliminate FcγR binding and ADCC/ADCP completely,where ADCC/ADCP effects can induce T-cell apoptosis and clearance and then compromise anti-tumor activity. 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 AK105-202 (NCT03866967) is a multicenter, single-arm, open-label study of penpulimab in metastatic NPC patients (pts) with disease progression after ≥2 prior lines of therapy including platinum-containing chemotherapy. All patients received penpulimab 200 mg q2w until progression or unacceptable toxicity. The primary endpoint was ORR based on RECIST v1.1 as assessed by an independent review committee (IRC). Key secondary endpoints included DCR, PFS, duration of response (DoR). Archived tissues were retrieved for the analysis of PD-L1 (Shuwen SAB-028). PD-L1 expression of tumor proportion score (TPS)≥50% was regarded as positive. Plasma Epstein-Barr virus DNA were obtained for biomarker correlative analysis.

Results As of 18 September 2020, the median follow-up was 7.9 months (range 0.9 to 16.9). The anti-tumor activity of penpulimab in the 111 pts with disease progression after ≥2 prior lines of therapy evaluable for efficacy (defined as pts who had an opportunity to be followed for at least 16 weeks and had measurable disease at baseline per RECIST v1.1) is shown in the table 1.

Treatment-related adverse events (TRAEs, including unlikely related) occurred in 79.2% of pts (≥G3 in 14.6% [19/130], treatment discontinuation in 3.1% [4/130]). Treatment-related SAEs occurred in 10.0% [13/130]. Most frequent TRAEs (≥10%) were fever (24.5%), hypothyroidism (24.6%), anemia (23.1%), ALT increased (17.0%) and WBC decreased (10.8%). Grade ≥3 TRAEs (≥2%) were hepatic function abnormal (2.3%) and anemia (2.3%).

Abstract 804 Table 1

Conclusions Penpulimab demonstrated encouraging anti-tumor activity and favorable safety profile in pts with disease progression after ≥2 prior lines of therapy. A higher proportion of objective responses was observed in NPC pts with PD-L1–positive tumors receiving penpulimab than those with PD-L1–negative tumors.

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