This is a phase Ib, open, mono-center, dose-escalation, tolerability and pharmacokinetic study evaluating the Recombinant Humanized Anti-PD-1 mAb for Injection in combination with Axitinib in patients with advanced kidney cancer and melanoma who have failed in routine systemic treatment.
This is a phase Ib, open, mono-center, dose-escalation, tolerability and pharmacokinetic study evaluating the Recombinant Humanized Anti-PD-1 mAb for Injection in combination with Axitinib in patients with advanced kidney cancer and melanoma who have failed in routine systemic treatment.The study will be conducted in 2 parts: dose escalation and cohort expansion. 18 to 24 patients will be enrolled in dose escalation part.This part is to analyze safety and efficacy of the humanized anti-PD-1 antibody in combination with axitinib and to confirm dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended dose (RD). After finishing the dose escalation part, we will enroll other patients for each tumor types of recommended dose group to ensure each group have 10 patients. This part is to further analyze safety and efficacy of the humanized anti-PD-1 antibody.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
humanized anti-PD-1 monoclonal antibody Toripalimab is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Safety assessments including vital signs, laboratory tests, and adverse event monitoring
Time frame: 3 years
PD-1 receptor occupancy of blood
To test the PD - 1 receptor share in the blood
Time frame: 3 years
Objective Response Rate (ORR) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine tumor response.
Time frame: 3 years
Duration of Response (DOR) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine duration of response.
Time frame: 3 years
Disease Control Rate (DCR) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine disease control rate.
Time frame: 3 years
Time to response (TTR) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine time to response.
Time frame: 3 years
Progression-free survival(PFS) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.
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Time frame: 3 years
Overall survival (OS) by irRC and RECIST 1.1
The treatment effect of JS001 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival.
Time frame: 3 years
PK Parameter: Maximum Plasma Concentration (Cmax)
Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb) in combination with axitinib
Time frame: 3 years
PK Parameter: Peak Time (Tmax)
Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: t1/2
t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Area Under the Curve (AUC)
Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Plasma clearance (CL)
Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Apparent volume of distribution (V)
Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Minimum Plasma Concentration (Cmin)
Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Average Plasma Concentration (Cav)
Average Plasma Concentration (Cav) of steady state after multiple dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: degree of fluctuation (DF)
degree of fluctuation (DF) of steady state after multiple dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years
PK Parameter: Apparent volume of distribution of steady state (Vss)
Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb in combination with axitinib
Time frame: 3 years