This is a phase I, open-label, multicentre study of MEDI4736 administered intravenously with a standard 3+3 dose-escalation phase to evaluate safety, tolerability, and pharmacokinetics in patients with advanced solid tumor followed by an expansion phase in patients with advanced solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
269
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
tremelimumab is administered by IV infusion every 4 weeks
Research Site
Beppu-shi, Japan
Research Site
Chūōku, Japan
Research Site
Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs)
Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.
Time frame: 90 days after the last dose of MEDI4736
Area under the concentration of MEDI4736 time curve
If data allow, noncompartmental PK parameter (AUC) will be estimated.
Time frame: Up to 90 days after the last dose of MEDI4736
Percentage of participants who developed detectable anti-drug antibodies (ADAs).
The immunogenic potential of MEDI4736 or tremelimumab will be assessed by summarizing the number percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Time frame: Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable.
Objective response rate (ORR)
Time frame: From first dose of study drug until death or up to 2 years
Maximum tolerated dose (MTD) or optimal biological dose (OBD)
maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible
Time frame: 90 days after the last dose of MEDI4736
Maximum concentration of MEDI4736
If data allow, noncompartmental PK parameter (Cmax) will be estimated.
Time frame: Up to 90 days after the last dose of MEDI4736
Clearance
If data allow, noncompartmental PK parameter (CL) will be estimated.
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Kashiwa, Japan
Research Site
Kitaadachi-gun, Japan
Research Site
Kōtoku, Japan
Research Site
Kure-shi, Japan
Research Site
Matsuyama, Japan
Research Site
Nagoya, Japan
Research Site
Osaka, Japan
Research Site
Sapporo, Japan
...and 11 more locations
Time frame: Up to 90 days after the last dose of MEDI4736
half-life after administration of MEDI4736
If data allow, noncompartmental PK parameter (t½) will be estimated.
Time frame: Up to 90 days after the last dose of MEDI4736
Disease control rate (DCR)
Time frame: From first dose of study drug until death or up to 2 years
Duration of response (DoR)
Time frame: From first dose of study drug until death or up to 2 years
Progression-free survival (PFS)
Alive and progression free at 6 months (APF6) and 12 months (APF12) will be obtained using the Kaplan-Meier plot of PFS.
Time frame: From first dose of study drug until death or up to 2 years
Overall survival (OS)
The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.
Time frame: From first dose of study drug until death or up to 2 years