LO12：慢性乙型肝炎患者的 HBsAg 丢失 皮下 PD-L1 抗体 ASC22 (ENVAF

StephenW

LO12：慢性乙型肝炎患者的 HBsAg 丢失
皮下 PD-L1 抗体 ASC22 (ENVAFOLIMAB) PLUSNUCLEOS(T)IDE 类似物治疗：来自 A 的中期结果
IIb 期临床试验
王贵强教授1、崔益民教授1、谢姚教授2、毛前国教授3、谢庆教授4、顾野教授5、教授
陈新月6、胡国新教授7、杨永峰博士8、卢家杰博士9、贵州邹教授10、张勤博士11、教授。
雷福12、陈永平博士13、郭晓琳博士14、侯金林教授15、颜月梅16、何邯博士16和何博士
Jinzi J. Wu16, (1)北京大学第一医院, (2)北京首都医科​​大学地坛医院, (3)厦门
上海交通大学医学院附属中医院（4）瑞金医院，
（5）沉阳第六人民医院，（6）首都医科大学佑安医院，（7）北京大学
深圳医院，（8）南京市第二医院，（9）四川大学华西医院，（10）
安徽医科大学第二附属医院、（11）上海同仁医院、（12）湘雅医院
中南大学、（13）温州医科大学第一附属医院、（14）温州医科大学第一医院
吉林大学、（15）南方医科大学南方医院、（16）歌礼生物科技有限公司
背景：阻断 PD-1/PD-L1 通路可能导致 HBV 的潜在治愈。 ASC22（Envafolimab）是一种
人源化单域 PD-L1 抗体皮下给药。在这里我们报告中期疗效和
ASC22 在慢性乙型肝炎 (CHB) 患者中的安全性数据。
方法：这项随机、单盲、多中心 IIb 期试验共招募了 149 名 CHB 患者（阴性
HBeAg 和 HBV DNA < 20 IU/ml) 在两个队列中进行 24 周不同剂量的 ASC22 和 24 周治疗
随访（NCT04465890）。在队列 1 中，75 名患者接受了 1 mg/kg ASC22 Q2W（n=60）或安慰剂治疗
(PBO) Q2W (n=15) + 核苷（酸）类似物（NA）。在以下患者中评估疗效和安全性
完成 1 mg/kg ASC22 (n=33) 或 PBO (n=11) + NAs 的 24 周治疗。
结果：ASC22 中位（范围）基线 HBsAg 水平分别为 2.7 (0.2~3.7) 和 2.7 (1.0~3.6) log10 IU/mL
和 PBO 团体。平均第 24 周 HBsAg 相对于基线的变化在 ASC22 和
PBO 团体。基线 HBsAg ≤ 500 IU/mL 接受 1 mg/kg ASC22+NAs 的患者（n=16）有更显着的
与接受 PBO+NAs 的患者相比，HBsAg 减少（-0.70 VS 0.00 log10 IU/mL，P < 0.01）。在患者中
基线 HBsAg ≤ 500 IU/mL，ASC22 组中有 7/16 (44%) 名患者达到 HBsAg，而 PBO 组中没有患者达到
减少 ≥ 0.5 log10 IU/mL。 3/16 (19%) 患者在第 4、16 周获得 HBsAg 消失（检测不到，< 0.05 IU/mL）
分别为 16 例和 16 例，直到治疗结束仍保持 HBsAg 阴性（图 1）。三名患者均维持
最后一次给药 ASC22 后 HBsAg 呈阴性。在 4/7 (57%) 和 2/3 (67%) 的患者中观察到 ALT 升高
HBsAg 减少分别≥ 0.5 log10 IU/mL 和 HBsAg 消失。接受 ASC22+NAs 治疗的患者有类似的 AE
与那些接受 PBO + NAs 治疗的人的档案。 79% (26/33) 和 82% (9/11) 报告了任何 AE 或 3 级 AE，
或 6% (2/33) 和 9% (1/11)，接受 ASC22+NAs 和 PBO+NAs 治疗的患者。治疗期间未发生 SAE。
PK 数据显示，ASC22 在稳态时的 Cmin 值预计在给药 1 个月后 > 3 μg/mL，
表明 > 90% 的受体占用率和 ASC22 有可能每月给予一次。结论：ASC22 Q2W 皮下给药 24 周显示安全且耐受性良好，并且
可诱导慢乙肝患者 HBsAg 下降，甚至 HBsAg 消失，尤其是基线 HBsAg ≤ 500 IU/mL 的患者。
当所有 149 名患者完成治疗和随访后，将进行进一步分析。

StephenW

LO12: HBsAg LOSS IN CHRONIC HEPATITIS B PATIENTS WITH
SUBCUTANEOUS PD-L1 ANTIBODY ASC22 (ENVAFOLIMAB) PLUSNUCLEOS(T)IDE ANALOGS TREATMENT: INTERIM RESULTS FROM A
PHASE IIb CLINICAL TRIAL
Prof. Guiqiang Wang1, Prof. Yimin Cui1, Prof. Yao Xie2, Prof. Qianguo Mao3, Prof. Qing Xie4, Prof. Gu Ye5, Prof.
Xinyue Chen6, Prof. Guoxin Hu7, Dr. Yongfeng Yang8, Dr. Jiajie Lu9, Prof. Guizhou Zou10, Dr. Qin Zhang11, Prof.
Lei Fu12, Dr. Yongping Chen13, Dr. Xiaolin Guo14, Prof. JinLin Hou15, Yuemei Yan16, Dr. Handan He16 and Dr.
Jinzi J. Wu16, (1)Peking University First Hospital, (2)Beijing  Ditan  Hospital  Capital  Medical  University, (3)Xiamen
Hospital  of Traditional  Chinese  Medicine, (4)Ruijin  Hospital, Shanghai Jiaotong University School of Medicine,
(5)Shenyang Sixth People's  Hospital, (6)Youan Hospital, Capital Medical University, (7)Peking University
Shenzhen Hospital, (8)The Second Hospital of Nanjing, (9)West China Hospital of Sichuan University, (10)The
Second Affiliated Hospital of Anhui Medical University, (11)Shanghai Tongren Hospital, (12)Xiangya Hospital of
Central South University, (13)The First Affiliated Hospital of Wenzhou Medical University, (14)The First Hospital of
Jilin University, (15)Nanfang Hospital, Southern Medical University, (16)Ascletis Bioscience Co., Ltd.
Background: Blockade of PD-1/PD-L1 pathway may lead to a potential cure for HBV. ASC22 (Envafolimab) is a
humanized single- domain PD-L1 antibody administered subcutaneously. Here we report the interim  efficacy and
safety data of ASC22 in patients  with chronic hepatitis B (CHB).
Methods: This  randomized, single-blind multi-center Phase IIb trial enrolled a total of 149 CHB patients  (negative
HBeAg and HBV DNA < 20 IU/ml) in two cohorts  for 24-week treatment of different dose of ASC22 and 24-week
follow-up (NCT04465890). In cohort 1, 75 patients were treated with 1 mg/kg ASC22 Q2W (n=60) or placebo
(PBO) Q2W (n=15) + Nucleos(t)ide Analogs (NAs). The efficacy and safety were assessed in patients  who
completed 24-week treatment of 1 mg/kg ASC22 (n=33) or PBO (n=11) + NAs.
Results: The median (range) baseline HBsAg levels  were 2.7 (0.2~3.7) and 2.7 (1.0~3.6) log10  IU/mL in ASC22
and PBO groups. Mean Week 24 HBsAg changes  from  baseline were -0.38 and 0.00 log10  IU/mL in ASC22 and
PBO groups. Patients  with baseline HBsAg ≤ 500 IU/mL receiving 1 mg/kg ASC22+NAs  (n=16) had more significant
HBsAg reduction compared to those receiving PBO+NAs  (-0.70 VS 0.00 log10 IU/mL, P < 0.01). In patients with
baseline HBsAg ≤ 500 IU/mL, 7/16 (44%) patients in ASC22 group compared to none in PBO group achieved HBsAg
reduction ≥ 0.5 log10 IU/mL. 3/16 (19%) patients obtained HBsAg loss (undetectable, < 0.05 IU/mL) at Week 4, 16
and 16, respectively, and remained HBsAg negative until the end of treatment (Fig.1). All three patients  maintained
HBsAg negative after last dosing of ASC22. ALT flares were observed in 4/7 (57%) and 2/3 (67%) patients with
HBsAg reduction ≥ 0.5 log10 IU/mL and HBsAg loss, respectively. Patients treated with ASC22+NAs had a similar AE
profile with those treated with PBO+NAs. Any AEs or Grade ≥ 3 AEs were reported in 79% (26/33) and 82% (9/11),
or 6% (2/33) and 9% (1/11), of patients treated with ASC22+NAs and PBO+NAs. No SAE occurred during treatment.
PK data showed that Cmin value of ASC22 at steady state was predicted to be > 3 μg/mL one month after dosing,
indicating > 90% receptor occupancy and ASC22 has  the potential to be given once monthly. Conclusion: Subcutaneous administration of ASC22 Q2W for 24 weeks is shown to be safe and well-tolerated, and
can induce HBsAg decline, even HBsAg loss, in CHB patients, especially in those with baseline HBsAg ≤  500 IU/mL.
Further analyses  will  be performed when all 149 patients complete treatment and follow-up.