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.
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.
Until August 2018, 18 subjects were enrolled, including 5 gastric cancer, 4 esophageal cancer, 2 Hodgkin’s lymphoma, 2 cervical cancer, and 1 each for rectum cancer, endometrial cancer, penile cancer, leiomyosarcoma and fibrosarcoma patients. The median dosing number was 5 (range: 1-12). No DLT was observed[JK1], and MTD was 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 TSH increased (11.1%). Possibly related Grade 3-4 TEAEs was observed in 2 subjects, one subject with haemoglobin decreased, leucopenia and thrombocytopenia, and the other one with haemoglobin decreased only. Pharmacokinetic analysis indicated the drug exposure was increased dose-dependently, with a half-life of 8.2 to 10.1 days. The T cell PD-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 (2 Hodgkin’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%.
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.
Guangzhou Gloria Biosciences Co., Ltd.
Guangzhou Gloria Biosciences Co., Ltd.
All authors have declared no conflicts of interest.