This is an open-label, multi-center phase 1 study. The trial, consisting of Part 1a dose confirmation and Part 1b dose expansion, is designed to evaluate the safety, tolerability, PK/PD and preliminary efficacy of HBM4003 in combination with pembrolizumab in patients with advanced NSCLC and other solid tumors.
subjects will be treated with HBM4003 in combination with pembrolizumab for up to 2 years or until confirmed disease progression, unacceptable tolerability or treatment discontinuation through withdrawal of consent occurs, whichever happens first. This trial consists of : * A screening period: 28 days * A treatment period: * Part 1a dose confirmation study * Part 1b dose expansion study * A post-treatment follow-up period, including * A safety follow-up period: 28 days after the last dose of study drug; * Post-treatment follow-up visit: day 84 after the last dose of study drug; * Survival follow-up.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
66
Subjects will be treated with HBM4003 and pembrolizumab on Day 1 during each 21-day cycles.
Part 1a: Number of subjects with DLT in each dose group within 1 cycles (21 days) after the first drug administration
DLT observation period was defined as one treatment cycles with a total of 21 days
Time frame: approximate 21 days
Part 1b: ORR
Proportion of subjects with complete response (CR) and partial response (PR)
Time frame: maximum 2 years
Part 1a: ORR
including proportions of subjects with complete response (CR) and partial response (PR)
Time frame: maximum 2 years
Part 1a: Disease Control Rate, DCR
including proportion of subjects with complete response (CR) and partial response (PR) and stable disease (SD)
Time frame: maximum 2 years
Part 1a: Duration of Response, DOR
Calculate the duration from the first confirmed CR or PR to the date of disease progression or death (for any reason)
Time frame: maximum 2 years
Part 1a: Duration of Disease Control, DDC
For subjects with Cr, PR or SD, the duration from the time of initial administration to the date of disease progression or death (for any reason) was calculated
Time frame: maximum 2 years
Cmax
Peak Plasma Concentration
Time frame: maximum 2 years
Tmax
Time to reach maximum serum concentration
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Time frame: maximum 2 years
AUC0-last
Area under the plasma concentration versus time curve from time zero to last
Time frame: maximum 2 years
AUC0-tau
Area under the serum concentration versus time curve from time zero to the dosing interval tau
Time frame: maximum 2 years
UC0-inf
Area under the serum concentration versus time curve from time zero to infinity
Time frame: maximum 2 years
Vss
Volume of distribution at steady state
Time frame: maximum 2 years
CL
Clearance
Time frame: maximum 2 years
t1/2
Terminal half-life
Time frame: maximum 2 years
Part 1a: Immunogenicity of HBM4003 and pembrolizumab
including the occurrence of positive anti-drug antibodies (ADA). The occurrence of neutralizing antibodies for subjects with positive ADA
Time frame: maximum 2 years
Part 1b: Number of subjects experiencing at least one treatment-related AE
Evaluate safety
Time frame: maximum 2 years
Part 1b: DCR
including proportion of subjects with CR, PR and SD
Time frame: maximum 2 years
Part 1b: DOR
calculate the duration from the first confirmed CR or PR to the date of disease progression or (for any reason) death.
Time frame: maximum 2 years
Part 1b: DDC
for subjects with CR, PR or SD, calculate the duration from the time of initial medication to the day of disease progression or (for any reason) death
Time frame: maximum 2 years
Part 1b: Overall survival (OS)
the length of time from the start of treatment to the death of the subject (for any reason)
Time frame: maximum 2 years
Part 1b: Progression-free survival (PFS)
the length of time from the beginning of treatment to the beginning of disease progression or death (for any reason)
Time frame: maximum 2 years
Part 1b: Immunogenicity of HBM4003 and pembrolizumab
including the occurrence of positive anti-drug antibodies (ADA). The occurrence of neutralizing antibodies for subjects with positive ADA.
Time frame: maximum 2 years