A Phase 1 study to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104.
This is a , Phase 1, first-in-human, multicenter, open label, dose escalation and dose expansion study designed to evaluate the safety, tolerability, PK, immunogenicity, pharmacodynamics, and preliminary antitumor activity of AK127 in combination with AK104 in subjects with advanced and metastatic solid tumours. The study comprises of 2 phases: a dose escalation phase and a dose expansion phase. Dose escalation for AK127 will occur using the 3+3+3 model given with a fixed regimen of AK104. Dose expansion will open at the discretion of the Sponsor.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Ashford Cancer Centre Research
Adelaide, Australia
Austin Health
Melbourne, Australia
Monash Health
Melbourne, Australia
Southside Cancer Care Centre
Sydney, Australia
The Kinghorn Cancer Centre, St Vincents Hospital Sydney
Incidence and Nature of 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 to 90 days after end of treatment
Number of participants with a Dose Limiting Toxicity (DLT)
DLTs will be assessed during the first treatment cycle and assessed as having a suspected relationship to study drug according to pre-specific criteria in the protocol.
Time frame: Within the first six weeks of treatment
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)
Progression-free survival is defined as the time from the start of treatment with AK127 + AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time frame: Up to 2 years
Progression-free survival (PFS)
Progression-free survival is defined as the time from the start of treatment 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 until death due to any cause.
Time frame: Up to 2 years
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Sydney, Australia
Area under the curve (AUC) of AK127+AK104 for assessment of pharmacokinetics
The endpoints for assessment of PK including serum concentrations of AK127+AK104 at different timepoints after treatment administration.
Time frame: From first dose of treatment through to 90 days after end of treatment
Maximum observed concentration (Cmax) of AK127 + AK104
The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.
Time frame: From first dose of treatment through to 90 days after end of treatment.
Minimum observed concentration (Cmin) of AK127+AK104
The endpoints for assessment of PK of AK127+AK104 include serum concentrations of AK127+AK104 at different timepoints after treatment administration.
Time frame: From first dose of treatment through to 90 days after end of treatment
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of AK127+AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Time frame: From first dose of treatment through to 90 days after end of treatment