This is an open-label, multicenter, dose-escalation phase I study to assess the safety, tolerability and preliminary efficacy of KN046 in participants with all advanced solid tumors who are not able to have current standard anti-tumor therapies. The purpose of this study is to determine the maximum tolerated dose (MTD) or a biological effective dose (BED), to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN046 as a single agent in adult participants with advanced solid tumors
Study Type
INTERVENTIONAL
Purpose
TREATMENT
Masking
NONE
Enrollment
21
The modified phase I "3 + 3" study design was used in dose escalation from low dose to high dose to determine the MTD.Sequential assignment of Patient cohorts to one of five dose levels of KN046: 0.3 mg/kg,1 mg/kg,3 mg/kg,5 mg/kg,10 mg/kg.
ICON Cancer Care
Southport, Queensland, Australia
RECRUITINGNumber of participants with dose limiting toxicity (DLT)
An DLT is defined as a ≥Grade 3 drug-related adverse event occurring within the first cycle (28 days) of dosing (excluding tumor flare causing local pain at sites of known or suspected tumor, localized rash, or a transient ≤Grade 3 infusion reaction) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
Time frame: During the first cycle (4 weeks) of treatment.
Number of participants with adverse events (AEs)
An AE is defined as any untoward medical occurrence in a participant administered KN046 and/or pharmaceutical product(s) 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 KN046,up to 2 years.
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: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Duration of response (DoR)
Duration of response is defined as the duration from the first documentation of objective response to the first documented 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 with KN046 until the first documentation of disease progression or death due to any cause, whichever occurs first.
Time frame: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Clinical benefit rate (CBR)
Clinical benefit rate is defined as the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD) to KN046 intervention.
Time frame: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Area under the curve (AUC) of KN046
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Time frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Maximum observed concentration (Cmax) of KN046
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Time frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Minimum observed plasma concentration (Ctrough) of KN046 at steady state
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Time frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Number of subjects who develop detectable anti-drug antibodies (ADAs)
The immunogenicity of KN046 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Time frame: Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.
Number of subjects who develop detectable neutralizing ADA (NADA)
The neutralizing ADA will be assessed by summarizing the number of subjects who develop detectable neutralizing ADA .
Time frame: Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.
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