This is a Phase 1, open-label study evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of MEDI5752 in Japanese patients with advanced solid solid tumors.
\<Objectives\> Primary Objective: To evaluate the safety and tolerability of MEDI5752 in Japanese subjects with advanced solid tumors. Secondary Objective: To assess the anti-tumor activity and efficacy of MEDI5752. To describe the pharmacokinetics of MEDI5752. Exploratory Objective: To conduct exploratory research into factors that may be predictive of response or may influence the progression of cancer and/or response (efficacy) to MEDI5752. Eligible patients will be administered as a single dose at each Cycle Day1. Each cycle from Cycle 1 has a duration of 21 days. A minimum of 3 and a maximum of 9 evaluable patients will be enrolled in each cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.
Research Site
Chūōku, Japan
Research Site
Kashiwa, Japan
The number of subjects experiencing treatment related adverse events (AEs)
The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v5.0.
Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
The number of subjects experiencing treatment related serious adverse events (SAEs)
The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v5.0.
Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
The number of subjects experiencing dose-limiting toxicities (DLTs)
The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.
Time frame: Up to 21 days following the first dose
The number of subjects experiencing abnormal laboratory evaluations
The primary endpoint is as assessed as the number of subjects experiencing changes in laboratory parameters from baseline.
Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
The number of subjects experiencing changes from baseline in vital signs reported as adverse events
The primary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.
Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events
The primary endpoint is as assessed by the the number of subjects experiencing clinically significant changes in ECG parameters from baseline.
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Time frame: From the time of informed consent through 90 days following termination of treatment with investigational product
Preliminary anti-tumor activitiy of MEDI5752 using Objective Response based on RECIST v1.1
The endpoints for assessment of antitumor activity is defined by using ORR, PFS, BOR,DCR, DoR and TTR according to RECIST v1.1.
Time frame: From the first dose of study drug through the date of documented progression, end of study, or date of death until study completion assessed up to 16 months.
Pharmacokinetics of MEDI5752
The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration. (e.g., Maximum plasma concentration\[Cmax\])
Time frame: At Cycle1Day1, ,Cycle1Day2, Cycle1Day3, Cycle1Day8, Cycle1Day15, Cycle2Day1, Cycle2Day8, Cycle3Day1, Cycle4Day1, Cycle5Day1, Cycle6Day1, Cycl7Day1, every 6 weeks after Cycle7Day1 (each cycle is 21 days) and up to 90 days following end of treatment.
Immunogenicity of MEDI5752
The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs)
Time frame: At Cycle1Day1, Cycle1Day8, Cycle1Day15, Cycle2Day1, Cycle2Day8, Cycle3Day1, Cycle4Day1, Cycle5Day1, Cycle6Day1, Cycl7Day1, every 6 weeks after Cycle7Day1 (each cycle is 21 days) and up to 90 days following end of treatment.
PD-L1 Expression in subjects with advanced solid tumors
The endpoint for the PD-L1 expression will be determined by Immunohistochemistry characterization.
Time frame: To be assessed at at baseline