MSB2311, an anti-programmed death-ligand 1 antibody, in advanced solid tumors and hematological malignancies: Safety and tolerability, early anti-cancer activities from a phase I study in Chinese patients.

Abstract

e15011 Background: 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. Methods: 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. Results: 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. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and hematological malignancies.