A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting PD-L1Protein in Patients With Advanced Solid Tumors (HLX20)
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|ClinicalTrials.gov Identifier: NCT03588650|
Recruitment Status : Completed
First Posted : July 17, 2018
Last Update Posted : June 3, 2022
|Condition or disease||Intervention/treatment||Phase|
|Advanced Solid Tumors||Drug: HLX20||Phase 1|
Tumor microenvironment plays an important role in the interaction of immune cells with cancer . The identification of programmed cell death receptor 1 (PD-1) and programmed death ligand-1 (PD-L1) have provided the scientific rationale and supports the clinical development of agents targeting this pathway. Currently, PD-1 and PD-L1 inhibitory pathway blockade has demonstrated impressive activity against a spectrum of multiple tumor types, including Hodgkin's lymphoma, melanoma, bladder cancer, lung cancer, renal cell carcinoma.
HLX20 is a novel anti-PD-L1 monoclonal antibody. In the nonclinical pharmacology studies, HLX20 has demonstrated anti-tumor activities in xenogenic animal models comparable to currently available anti-PD-L1 monoclonal antibodies. HLX20 binds to PD-1 and PD-L1 inhibitory pathway and human PD-L1 at high affinity, and mouse PD-L1 at much lower affinity. HLX20 does not cause hemolysis to human red blood cells and has no local irritation to human tissues. (The results of pharmacokinetic (PK)/toxicokinetic studies in cynomolgus studies have been described in detail in the Investigator's Brochure.)The no-observable adverse effect level (NOAEL) is set at 100 mg/kg every 2 weeks for 13 weeks in cynomolgus studies.
Based on these results, the initial dose 1 mg/kg every 2 weeks was chosen for this study .This dose level is approximately 30-fold lower than the human equivalent dose of NOAEL from preclinical toxicology studies. An adaptive Bayesian dose-finding design will be used to identify the MTD (maximum tolerated dose). The target toxicity rate for the MTD is set at 0.3 and the maximum sample size is 30.The safety profiles at different dose levels, PK parameters, biomarkers, pharmacodynamic markers, immunogenicity as well as the preliminary efficacy of the drug, will also be investigated in this study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||26 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of HLX20, a Human Monoclonal Antibody Targeting Programmed Death Ligand 1 (PD-L1) Protein in Patients With Advanced Solid Tumors|
|Actual Study Start Date :||August 7, 2018|
|Actual Primary Completion Date :||June 28, 2021|
|Actual Study Completion Date :||June 28, 2021|
Experimental: HLX20, in patients with solid tumors
Each cycle of treatment consists of 4 weeks. Patients who enroll into this study will receive an infusion of assigned dose of HLX20 once every two weeks. No intra-patient dose escalation is allowed. The proposed dose escalation sequence is 1, 3, 10 and 20 mg/kg, starting from 1 mg/kg.
a Human Monoclonal Antibody Targeting Programmed Death Ligand-1 (PD-L1) Protein
- Maximum tolerated dose of HLX20 in solid tumors patients [ Time Frame: 1 year ]The target toxicity rate in this study for the MTD is set at 0.3 ( 30% DLT) identified by an adaptive Bayesian dose-finding design .
- Maximum serum concentration (Cmax) of HLX20. [ Time Frame: 1 year ]
- Minimum serum concentration (Cmin) of HLX20. [ Time Frame: 1 year ]
- Area under serum concentration-time curve within one dosing interval (AUC0-tau) of HLX20. [ Time Frame: 1 year ]
- Terminal elimination half-life (T1/2) of HLX20 in different cohorts [ Time Frame: 1 year ]
- Clearance rate (CL) of HLX20 [ Time Frame: 1 year ]
- Volume of distribution at steady state (Vss) of HLX20. [ Time Frame: 1 year ]
- Immunogenicity [ Time Frame: 1 year ]The presence and percentage of anti-HLX20 antibody
- Disease control rate (DCR) [ Time Frame: 1 year ]Number of patients with complete response/partial response/stable disease divided by the total number of patients treated
- Overall response rate (ORR). [ Time Frame: 1 year ]Number of patients with confirmed complete or partial response, divided by the total number of treated patients with measurable disease at baseline
- Receptor occupancy of PD-L1 on human T-cells. [ Time Frame: 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03588650
|Australia, New South Wales|
|Kinghorn cancer centre|
|Darlinghurst, New South Wales, Australia, 2010|
|Darlinghurst, New South Wales, Australia, 2109|
|Sunshine Coast University Hospital|
|Brisbane, Queensland, Australia, 4000|
|Gold Coast Hospital|
|Southport, Queensland, Australia, 4215|
|Australia, South Australia|
|CMAX Clinical research|
|Adelaide, South Australia, Australia, 5000|
|Melbourne, Victoria, Australia, 3144|