Shi Yuankai, Zhou Keshu, Zhou Hui, Qin Yan, Jing Hongmei, Xiang Ying, Wang Zhao, Wang Zhen, Zang Aimin, Bai Ou, Li Zhenyu, Zhang Huilai, Song Yongping, Liang Jinjin, Wei Min
Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Hematology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
EClinicalMedicine. 2024 Jun 20;73:102702. doi: 10.1016/j.eclinm.2024.102702. eCollection 2024 Jul.
MIL62, a novel glycoengineered type Ⅱ anti-CD20 monoclonal antibody, with a nearly completely afucosylated N-glycans in Fc region, has demonstrated superior activity compared with rituximab and obinutuzumab in vitro and in vivo, respectively.
This multicentre, single-arm, phase 1b/2 trial aimed to explore the efficacy, pharmacokinetics, and safety of MIL62 combined with lenalidomide in patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Eligible patients included those who had histopathologically confirmed CD20 positive FL (grade 1-3a) or MZL and failed to be treated with rituximab. Patients received intravenously infused MIL62 1000 mg (cycle 1: day 1, 15; cycles 2-8: day 1, cycles 10 and 12: day 1) combined with oral lenalidomide (once a day, days 2-22, the initial dose was 10 mg, and the maximum dose was 20 mg) for 12 cycles, 28 days as a cycle. The primary endpoint was objective response rate (ORR) assessed by investigator per Lugano 2014 criteria every 3 cycles. This study was registered in ClinicalTrials.gov (NCT04110301).
Between November 22, 2019 and December 22, 2020, 54 patients were enrolled from 11 hospitals in China and received study treatment. Fifty patients were included in the efficacy analysis set, and 43 patients (86%, 95% CI: 73, 94) achieved objective response, meeting the pre-specified primary endpoint. Disease control rate was 96% (48/50, 95% CI: 86, 100), proportion of patients with duration of response (DoR) > 6 months was 77% (33/43). The median follow-up for survival was 12.3 months (IQR 12.0-12.6). The 1-year progression-free survival rate was 72% (95% CI: 57, 83), 9-month DoR rate was 74% (95% CI: 58, 85), and 1-year overall survival rate was 98% (95% CI: 85, 100). Most common TRAEs were neutropenia (93%, 50/54), leukopenia (85% 46/54), thrombocytopenia (61% 33/54), lymphopenia (32% 17/54), and alanine aminotransferase increased (20% 11/54).
MIL62 combined with lenalidomide showed promising efficacy in patients with R/R FL and MZL. A multicentre, randomized, open-label, phase Ⅲ trial of MIL62 combined with lenalidomide versus lenalidomide in anti-CD20 monoclonal antibody refractory FL patients is ongoing (NCT04834024).
Beijing Mabworks Biotech Co. Ltd, Beijing China and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).
MIL62是一种新型的糖基工程化Ⅱ型抗CD20单克隆抗体，其Fc区域的N聚糖几乎完全去岩藻糖基化，分别在体外和体内显示出优于利妥昔单抗和奥妥珠单抗的活性。
这项多中心、单臂、1b/2期试验旨在探索MIL62联合来那度胺治疗复发/难治性（R/R）滤泡性淋巴瘤（FL）或边缘区淋巴瘤（MZL）患者的疗效、药代动力学和安全性。符合条件的患者包括组织病理学确诊为CD20阳性FL（1-3a级）或MZL且未接受利妥昔单抗治疗的患者。患者静脉输注MIL62 1000mg（第1周期：第1天、第15天；第2-8周期：第1天，第10和12周期：第1天）联合口服来那度胺（每日1次，第2-22天，初始剂量为10mg，最大剂量为20mg），共12个周期，每28天为一个周期。主要终点是研究者根据2014年卢加诺标准每3个周期评估的客观缓解率（ORR）。本研究已在ClinicalTrials.gov注册（NCT04110301）。
2019年11月22日至2020年12月22日，中国11家医院共纳入54例患者并接受研究治疗。50例患者纳入疗效分析集，43例患者（86%，95%CI：73，94）达到客观缓解，达到预先设定的主要终点。疾病控制率为96%（48/50，95%CI：86，100），缓解持续时间（DoR）>6个月的患者比例为77%（33/43）。生存的中位随访时间为12.3个月（IQR 12.0-12.6）。1年无进展生存率为72%（95%CI：57，83），9个月DoR率为74%（95%CI：58，85），1年总生存率为98%（95%CI：85，100）。最常见的治疗相关不良事件为中性粒细胞减少（93%，50/54）、白细胞减少（85%，46/54）、血小板减少（61%，33/54）、淋巴细胞减少（32%，17/54）和丙氨酸转氨酶升高（20%，11/54）。
MIL62联合来那度胺在R/R FL和MZL患者中显示出有前景的疗效。一项关于MIL62联合来那度胺对比来那度胺治疗抗CD20单克隆抗体难治性FL患者的多中心、随机、开放标签Ⅲ期试验正在进行中（NCT04834024）。
北京迈邦生物科技有限公司，中国北京以及国家重大新药创制科技重大专项（2017ZX09304015）
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