創勝集團 - 全整合型國際化生物制藥公司
創勝集團, 生物藥, 抗體, 藥物研發
29 May, 2020
Xichun Hu, Jifang Gong, Dongmei Ji, Lin Shen, Yufeng Li, Mengde Wang, Yingjie Huang, Zhenzhong Xia, Lingmin Lu, John Huang, Li Xu, Jenny Li, Yuntao Wan, Xueming Qian
Fudan University Shanghai Cancer Center, Shanghai, China, Gastrointestinal Medical Oncology, Beijing Cancer Hospital, Beijing, China, Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China, Mabspace Biosciences Co Ltd, Suzhou, NJ, China, Mabspace Biosciences Co Ltd, Suzhou, China
MSB2311 is a novel humanized programmed death-ligand 1 (PD-L1) antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration.
Patients with metastatic solid tumors and selected hematological malignancies progressed after standard treatments were enrolled in this Phase I study. In dose escalation part, MSB2311 was given at levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, either EBV positive, PD-L1 positive, MSI-High or TMB-High, were enrolled and dosed either in 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD/MAD and RP2D. Secondary objectives include the assessment of pharmacokinetics, immunogenicity, and preliminary efficacy per RECIST1.1.
At data cut-off at Jan 19, 2020, 27 Chinese patients have been treated, 18 (66.7%) of them received at least 4 cycles of MSB2311. No dose limiting toxicity was reported and MTD has not been identified. The most common treatment-emergent adverse events (TEAEs) ( > 10%) included: anemia, hypothyroidism, hyperglycemia, hypertriglyceridemia, nausea, vomiting, fatigue, malaise, pyrexia and cough. Eleven patients (40.7%) experienced Grade 3 TEAEs, and 6 patients (22.2%) experienced SAEs. One lymphoma patient experienced grade 4 hypercalcemia and platelet count decreased, which were assessed as related to study drug by the investigator. MSB2311 displayed a linear pharmacokinetic profile with calculated T1/2 of about 10-13 days. Among 18 evaluable patients treated with 20 mg/kg Q3W, the best response of PR was observed in 4 out of 12 patients with solid tumors including NSCLC, NPC and Gastric cancer, and 1 out of 6 patients with lymphoma. The mean duration of response was 127 (range 38-278) days.
MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and hematological malignancies.