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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01938612

Collaborator

(none)

269

Enrollment

Locations

Arms

86.4

Actual Duration (Months)

12.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: MEDI4736 Drug: tremelimumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

269 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 12, 2013

Actual Primary Completion Date :

Mar 1, 2018

Actual Study Completion Date :

Nov 25, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI4736 Q2W Evaluate MEDI4736 given every 2 weeks	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Q3W Evaluate MEDI4736 given every 3 weeks	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Dose Expansion evaluate MEDI4736 given every 2 weeks	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 Q4W Evaluate MEDI4736 given every 4 weeks	Drug: MEDI4736 MEDI4736 will be administered by IV infusion every 14, 21 or 28 days.
Experimental: MEDI4736 combined with another drug evaluate MEDI4736 in combination with another drug given every 4 weeks	Drug: tremelimumab tremelimumab is administered by IV infusion every 4 weeks

Outcome Measures

Primary Outcome Measures

Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs) [90 days after the last dose of MEDI4736]
Safety profile will be assessed through number of participants experiencing adverse events (AEs), serious adverse events (SAEs), laboratory evaluations, vital signs, and physical examinations.

Secondary Outcome Measures

Area under the concentration of MEDI4736 time curve [Up to 90 days after the last dose of MEDI4736]
If data allow, noncompartmental PK parameter (AUC) will be estimated.
Percentage of participants who developed 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.]
The immunogenic potential of MEDI4736 or tremelimumab will be assessed by summarizing the number percentage of subjects who develop detectable anti-drug antibodies (ADAs).
Objective response rate (ORR) [From first dose of study drug until death or up to 2 years]
Maximum tolerated dose (MTD) or optimal biological dose (OBD) [90 days after the last dose of MEDI4736]
maximum tolerated dose (MTD) or optimal biological dose (OBD) of MEDI4736, if possible
Maximum concentration of MEDI4736 [Up to 90 days after the last dose of MEDI4736]
If data allow, noncompartmental PK parameter (Cmax) will be estimated.
Clearance [Up to 90 days after the last dose of MEDI4736]
If data allow, noncompartmental PK parameter (CL) will be estimated.
half-life after administration of MEDI4736 [Up to 90 days after the last dose of MEDI4736]
If data allow, noncompartmental PK parameter (t½) will be estimated.
Disease control rate (DCR) [From first dose of study drug until death or up to 2 years]
Duration of response (DoR) [From first dose of study drug until death or up to 2 years]
Progression-free survival (PFS) [From first dose of study drug until death or up to 2 years]
Alive and progression free at 6 months (APF6) and 12 months (APF12) will be obtained using the Kaplan-Meier plot of PFS.
Overall survival (OS) [From first dose of study drug until death or up to 2 years]
The proportion of patients alive at 12 months will be obtained from the Kaplan-Meier plot of OS.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 130 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Research Site	Beppu-shi	Japan	874-0011
2	Research Site	Chuo-ku	Japan	104-0045
3	Research Site	Kashiwa	Japan	277-8577
4	Research Site	Kitaadachi-gun	Japan	362-0806
5	Research Site	Koto-ku	Japan	135-8550
6	Research Site	Kure-shi	Japan	737-0023
7	Research Site	Matsuyama-shi	Japan	791-0280
8	Research Site	Nagoya-shi	Japan	464-8681
9	Research Site	Osaka-shi	Japan	541-8567
10	Research Site	Osakasayama	Japan	589-8511
11	Research Site	Sapporo-shi	Japan	003-0804
12	Research Site	Sapporo-shi	Japan	060-8648
13	Research Site	Suita-shi	Japan	565-0871
14	Research Site	Sunto-gun	Japan	411-8777
15	Research Site	Takatsuki-shi	Japan	569-8686
16	Research Site	Yokohama-shi	Japan	241-8515
17	Research Site	Seoul	Korea, Republic of	03080
18	Research Site	Seoul	Korea, Republic of	135-710
19	Research Site	Tainan	Taiwan	704
20	Research Site	Taipei	Taiwan	10002
21	Research Site	Taoyuan	Taiwan	333