A novel recombinant human anti-PD-1 monoclonal antibody GLS-010 in patients with advanced cancer: Result of a phase Ia clinical trial

Abstract

Background: GLS-010 is a novel recombinant fully human anti-programmed cell death protein 1 (PD-1) monoclonal antibody. This phase Ia study was to primarily evaluate the safety and tolerance profile of GLS-010 and to identify a proper dose. Methods: A 3+3 dose escalation design was applied. GLS-010 was given at 1mg/kg 4mg/kg and 10mg/kg respectively once every 2 weeks. An exploratory cohort with 240mg fixed dosage was also conducted along with the 10mg/kg cohort. Results:Until August 2018, 18 subjects were enrolled, including 5 gastric cancer, 4 esophageal cancer, 2Hodgkin's lymphoma, 2 cervical cancer, and 1 each for rectumcancer, endometrial cancer, penile cancer, leiomyosarcoma and fibrosarcoma patients. The median dosing number was 5 (range: 1-12).NoDLT was observed[JK1], andMTDwas not reached. Related treatment emergent adverse event (TEAE)s included haemoglobin decreased (61.1%), blood bilirubin increased (22.2%), fatigue (16.7%), diarrhea (11.1%) decreased appetite (11.1%), neutropenia (11.1%), protein urine present (11.1%), blood creatine kinase increased (11.1%), leukopenia (11.1%) and blood TSHincreased (11.1%). Possibly relatedGrade 3-4 TEAEs was observed in 2 subjects, one subject with haemoglobin decreased, leucopenia and thrombocytopenia, and the other onewith haemoglobin decreased only. Pharmacokinetic analysis indicated the drug exposure was increased dosedependently with a half-life of 8.2 to 10.1 days. The T cellPD-1 receptor occupancy (RO) rate was over 80%and no anti-drug antibody (ADA) was detected for all subjects. Partial response (PR) was observed in 5 subjects (2Hodgkin's lymphoma, 1 gastric cancer, 1 cervical cancer and 1 penile cancer patients). Stable disease (SD) was observed with 1 subject (endometrial cancer). The objective response rate (ORR) was assessed to be 27.8%, and the disease control rate (DCR) was 33.3%. Conclusions: GLS-010 demonstrated acceptable safety and tolerance, and preliminary efficacy in patients with advanced cancer. A 240mg fixed dosing regimen is currently recommended for further clinical study.