This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in Japanese patients with advanced and metastatic solid tumor. The dose escalation will follow the widely used 3+3 design.
This is an open label, dose escalation study to evaluate the safety and tolerability of KN035 in Japanese patients with advanced and metastatic solid tumor. The dose escalation will follow the widely used 3+3 design. Cohorts of 3-6 subjects will be enrolled sequentially at escalating doses of 1.0, 2.5, 5.0 and 10 mg/kg weekly. Dose escalation will continue until identification of MTD up to a maximum dose of 10 mg/kg. MTD is defined as the highest dose studied at which no more than 1 of 6 subjects has experienced a dose-limiting toxicity (DLT) in Cycle 1. The enrolled patients are managed under hospitalization for DLT observation period (C1 28 days). If no DLTs occur in a cohort of 3 subjects, a new cohort of 3 subjects will be treated at the next higher dose level. If 1 of 3 subjects in a cohort experiences a DLT, that cohort will be expanded to 6 subjects. If only 1 of the 6 subjects has a DLT, then the next cohort of 3 subjects will be treated at the next higher dose level. If 2 or more DLTs occur within a cohort, then that dose level will be above the MTD, and the previous lower (tolerated) dose level will be considered the MTD if ≤ 1 in 6 subjects has a DLT. A subject who withdraws from the study during Cycle 1 for reasons other than a DLT will be replaced. Subjects will be monitored for safety and efficacy throughout the study. After radiological tumor assessment at Screening, the first radiological assessment of tumor response status will be performed at Week 12 (± 1 week), unless there is clinical indication warranting earlier radiologic imaging. The same imaging technique used at baseline has to be used throughout the study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Four cohorts dosed at 1.0 mg/kg, 2.5 mg/kg, 5.0 mg/kg, and 10 mg/kg weekly. All cohorts are administered by subcutaneous injection (SC).
St. Marianna University School of Medicine Hospital
Kawasaki, Japan
National Cancer Center Hospital
Tokyo, Japan
Incidence of dose limiting toxicities
Time frame: From screening to up to cycle 1 (28 days)
KN035 safety and tolerability assessed by monitoring AEs per the NCI-CTC-AE Version 4.03, physical examination, electrocardiograms, laboratory measurements and severity of adverse events
The safety of KN035 will be assessed throughout the study by monitoring adverse events (AEs) per the NCI-CTC-AE Version 4.03, physical examination, electrocardiograms, laboratory measurements and severity of adverse events.
Time frame: From screening to up to 1 months after the last dose of study drug (up to approximately 2 years
Peak Plasma Concentration (Cmax) of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Peak Time (Tmax) of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Area under the plasma concentration versus time curve (AUC) of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
t1/2 of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Trough concentration of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Plasma clearance (CL) of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Apparent volume of distribution of KN035 in Japanese patients
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Time frame: From Pre-dose of the first dose to up to 48 weeks
Accumulation rate of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Anti-Drug Antibody of KN035 in Japanese patients
Time frame: From Pre-dose of the first dose to up to 48 weeks
Changes of lymphocyte Subtyping
Time frame: From Pre-dose of the first dose to up to 48 weeks
Changes of cytokine
Time frame: From Pre-dose of the first dose to up to 6 months
Objective Response Rate (ORR)
Time frame: Up to 2 approximately years
Disease Control Rate (DCR)
Time frame: Up to 2 approximately years
Progression-Free survival (PFS)
Time frame: Up to 2 approximately years
Duration of Response (DOR)
Time frame: Up to 2 approximately years