A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours

Advanced Solid Tumors Clinical Trial

Official title:

A Phase I, Open-Label, Multicentre Study to Evaluate the Safety, Tolerability and Pharmacokinetics of MEDI4736 in Patients With Advanced Solid Tumours

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01938612
• Other study ID #: D4190C00002
• Status: Completed
• Phase: Phase 1
• Start date: September 12, 2013
• Est. completion date: November 25, 2020

Study information

• Verified date: March 2021
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 269
• Est. completion date: November 25, 2020
• Est. primary completion date: March 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 130 Years

Eligibility

Inclusion Criteria:

• In the dose-escalation phase: patients with advanced solid tumors refractory to standard treatment, intolerant of standard treatment, or for which no standard therapy exists.

In the dose-expansion phase: histologically- or cytologically-confirmed advanced or metastatic biliary tract cancer (BTC), esophagus cancer(EC) (squamous cell carcinoma) or squamous cell carcinoma of the head and neck (SCCHN). - men or women. - Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. - Adequate organ and marrow function. - Subjects must have at least 1 measurable lesion. - Available archived tumor tissue sample. - Willingness to provide consent for biopsy samples.

Exclusion Criteria:

• Any prior Grade = 3 irAE while receiving immunotherapy - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Active or prior documented autoimmune disease within the past 2 years - History of primary immunodeficiency - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment - Women who are pregnant or lactating - Uncontrolled intercurrent illness - Known history of tuberculosis - Known to be human immunodeficiency virus (HIV) positive - Hepatitis B or C infection - Other invasive malignancy within 5 years

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• MEDI4736
MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
• tremelimumab
tremelimumab is administered by IV infusion every 4 weeks

Locations

Country	Name	City	State
Japan	Research Site	Beppu-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Kashiwa
Japan	Research Site	Kitaadachi-gun
Japan	Research Site	Koto-ku
Japan	Research Site	Kure-shi
Japan	Research Site	Matsuyama-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Osaka-shi
Japan	Research Site	Osakasayama
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Suita-shi
Japan	Research Site	Sunto-gun
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	90 days after the last dose of MEDI4736
Secondary	Area under the concentration of MEDI4736 time curve	If data allow, noncompartmental PK parameter (AUC) will be estimated.	Up to 90 days after the last dose of MEDI4736
Secondary	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).	Up to 6 months after the last dose of MEDI4736 or up to 1 month after the last dose of tremelimumab where applicable.
Secondary	Objective response rate (ORR)		From first dose of study drug until death or up to 2 years
Secondary	Maximum tolerated dose (MTD) or optimal biological dose (OBD)	maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible	90 days after the last dose of MEDI4736
Secondary	Maximum concentration of MEDI4736	If data allow, noncompartmental PK parameter (Cmax) will be estimated.	Up to 90 days after the last dose of MEDI4736
Secondary	Clearance	If data allow, noncompartmental PK parameter (CL) will be estimated.	Up to 90 days after the last dose of MEDI4736
Secondary	half-life after administration of MEDI4736	If data allow, noncompartmental PK parameter (t½) will be estimated.	Up to 90 days after the last dose of MEDI4736
Secondary	Disease control rate (DCR)		From first dose of study drug until death or up to 2 years
Secondary	Duration of response (DoR)		From first dose of study drug until death or up to 2 years
Secondary	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.	From first dose of study drug until death or up to 2 years
Secondary	Overall survival (OS)	The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.	From first dose of study drug until death or up to 2 years