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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: tremelimumab; Drug: MEDI4736

Study type: Interventional

Funder types: Industry

Identifiers

NCT01938612

D4190C00002

Details and patient eligibility

About

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.

Enrollment: 269 patients

Sex: All

Ages: 20 to 130 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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269 participants in 5 patient groups

MEDI4736 Q2W

Experimental group

Description:

Evaluate MEDI4736 given every 2 weeks

Treatment:

Drug: MEDI4736

MEDI4736 Q3W

Experimental group

Description:

Evaluate MEDI4736 given every 3 weeks

Treatment:

Drug: MEDI4736

MEDI4736 Dose Expansion

Experimental group

Description:

evaluate MEDI4736 given every 2 weeks

Treatment:

Drug: MEDI4736

MEDI4736 Q4W

Experimental group

Description:

Evaluate MEDI4736 given every 4 weeks

Treatment:

Drug: MEDI4736

MEDI4736 combined with another drug

Experimental group

Description:

evaluate MEDI4736 in combination with another drug given every 4 weeks

Treatment:

Drug: tremelimumab