The purpose of the study is to evaluate the safety and tolerability of HLX60 combined with HLX10 in order to determine the maximum tolerated dose (MTD) and Recommended Phase 2 dose (RP2D) and to evaluate the preliminary efficacy for each combination regimen.
Accelerated titration and "3 + 3" dose escalation were used in this trial . various doses of HLX60(anti-GARP) combined with HLX10(anti-PD-1) by intravenous infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
five various doses of HLX60 combined with flat dose of HLX10
Macquarie University Hospital & Nepean Hospital
Sydney, Australia
Adverse event
Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for patients receiving study drug.
Time frame: Through study completion, assessed up to 2 years.
Incidence of DLT
Ratio of the number of patients with DLT events in each dose group to the number of patients in the dose group during the DLT evaluation period.
Time frame: Up to 3 weeks.
MTD
The maximum tolerated dose (MTD) of HLX60 combined with HLX10
Time frame: Up to 3 weeks.
RP2D
The recommended phase II dose (RP2D) of HLX60 combined with HLX10
Time frame: Through study completion, assessed up to 2 years.
Objective response rate (ORR)
Percentage of patients with complete response or partial response determined by investigators according to RECIST v1.1
Time frame: Through study completion, assessed up to 2 years.
Progression-free survival (PFS)
PFS is defined as the time from the first administration of HLX60 and HLX10 to the first occurrence of disease progression or death due to any cause, whichever occurs first.
Time frame: Through study completion, assessed up to 2 years.
Overall survival(OS)
OS is defined as the time from the first administration of HLX60 to death due to any cause.
Time frame: Through study completion, assessed up to 2 years.
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Cmax
serum concentration (Cmax)
Time frame: 1 year
Tmax
time to reach Cmax (Tmax)
Time frame: 1 year
t1/2
elimination half-life (t1/2)
Time frame: 1 year
AUC
area under the serum concentration-time curve (AUC)
Time frame: 1 year
PD
include the GARP receptor occupancy on Treg cells, tumor infiltrating lymphocytes (TILs), FOXP3, pSMAD 2/3 in tumor tissues.
Time frame: 1 year
immunogenicity of HLX60
Incidence of HLX60 anti-drug antibody (ADA) and neutralizing antibody (NAb)
Time frame: 1 year
Potential prognostic and predictive biomarkers
include the expressions of GARP, PD-L1 in tumor tissues and soluble GARP in peripheral blood.
Time frame: 1 year