This is a Phase 1+2, open-label, dose-escalation, and multidose study, aiming to investigate the safety, tolerability and pharmacokinetics of ZKAB001 (a fully human monoclonal antibody targeting the Programmed Death - Ligand 1 (PD-L1) membrane receptor on T lymphocytes and other cells of the immune system) administered every 14 days in subjects with limited stage of high-grade osteosarcoma of maintenance therapy after adjuvant chemotherapy.
The study will consist of 4 periods: Screening (up to 28 days), Lead-in period (Day -28), Treatment (up to 24 cycles or 1 year, whichever occurs first), and Follow-up (up to 2 years). There will be a lead-in period on Day -28 for each dose escalation cohort in which the single-dose pharmacokinetics(PK) of ZKAB001 will be characterized prior to initiation of continuous dosing in the first cycle of treatment. The lead-in period duration, PK time-points, doses and/or regimens used in subsequent cohorts may be modified based on the exposure (AUC) observed during the lead-in period (although the number of PK samples will not be increased). Treatment of continuous dosing is up to 24 cycles or 1 year, until as per investigator's opinion, subjects experience disease progression (evaluated by RECIST 1.1), no clinical benefit, or intolerable toxicity. If investigators suspect subjects experience pseudoprogression or has evidence to prove "mixed response", subjects can continue to accept treatment as investigator decided.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
5mg/kg/times bi-week IV administration of ZKAB001
10mg/kg/times bi-week IV administration of ZKAB001
15mg/kg/times bi-week IV administration of ZKAB001
Shanghai Sixth People's Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGDose limiting toxicity (DLT)
Adverse events of level 3 or above related to the study drug occurring within 28 days after the first dose as assessed by CTCAE v4.0.
Time frame: 28 days after first dose
Maximal tolerable dose(MTD)
DLT occurs in less than 1/6 subjects, this lower dose is defined as MTD.
Time frame: 28 days after first dose
EFS(event-free survival)
The rate of 3-year event-free survival
Time frame: through study completion, an average of 3 years
AUC(0-t)
Area under curve 0-t
Time frame: 24 periods or 1 year
AUC(INF)
Area under curve INF
Time frame: 24 periods or 1 year
Cmax
Peak concentration
Time frame: 24 periods or 1 year
Tmax
Peak time
Time frame: 24 periods or 1 year
T1/2
Half life
Time frame: 24 periods or 1 year
Vss
Steady-state apparent volume of distribution based on plasma concentration
Time frame: 24 periods or 1 year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
total body clearance(CLT)
total body clearance
Time frame: 24 periods or 1 year
Cmin
The trough value at steady state
Time frame: 24 periods or 1 year
the percentage of the receptors of PD-L1 in CD14+ monocytes and CD3+T cells
To detected the percentage of the receptors of PD-L1 in CD14+(cluster of differentiation 14+ ) monocytes and CD3+(cluster of differentiation 3+)T cells.
Time frame: through study completion, an average of 3 years
the number of subjects presenting detectable anti drug antibodies (ADAs)
To evaluated the number of subjects presenting detectable anti drug antibodies (ADAs).
Time frame: through study completion, an average of 3 years