This study is to characterize the safety, tolerability, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK105 as a single agent in adult subjects with advanced solid tumor malignancies. The study consists of a dose escalation phase (Phase 1a) to determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D) for AK105 as a single agent, and a dose expansion phase (Phase 1b) in subjects with specific tumor types which will characterize treatment of AK105 as a single agent at the MTD or RP2D.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
99
Anti-PD-1 monoclonal antibody; Subjects will receive AK105 by intravenous administration.
St Vincent's Hospital, Sydney (The Kinghorn Cancer Centre)
Darlinghurst, New South Wales, Australia
Border Medical Oncology
East Albury, New South Wales, Australia
Liverpool Hospital
Liverpool, New South Wales, Australia
ICON Cancer Foundation
South Brisbane, Queensland, Australia
Ashford Cancer Centre Research
Adelaide, South Australia, Australia
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: From the time of informed consent signed through 90 days after the last dose of AK105
Number of participants with a Dose Limiting Toxicity (DLT)
DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment.
Time frame: During the first 4 weeks
Objective response rate (ORR)
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Time frame: Up to 2 years
Disease control rate (DCR)
The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
Time frame: Up to 2 years
Progression-free survival (PFS)
Progression-free survival is defined as the time from the start of treatment with AK105 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 2 years
Overall survival (OS)
Overall survival is defined as the time from the start of treatment with AK105 until death due to any cause.
Time frame: Up to 2 years
Area under the curve (AUC) of AK105
The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.
Time frame: From first dose of AK105 through 30 days after last dose of AK105
Maximum observed concentration (Cmax) of AK105
The endpoints for assessment of PK of AK105 include serum concentrations of AK105 at different timepoints after AK105 administration.
Time frame: From first dose of AK105 through 30 days after last dose of AK105
Minimum observed concentration (Cmin) of AK105 at steady state
The endpoints for assessment of PK of AK105 include serum concentrations of
Time frame: From first dose of AK105 through 30 days after last dose of AK105
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of AK105 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
Time frame: From first dose of AK105 through to 90 days after last dose of AK105
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