Overview

This trial is active, not recruiting.

Condition advanced solid tumors
Treatment medi4736
Phase phase 1/phase 2
Target PD-1
Sponsor MedImmune LLC
Start date August 2012
End date July 2017
Trial size 1022 participants
Trial identifier NCT01693562, CD-ON-MEDI4736-1108

Summary

This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced solid tumors followed by an expansion phase in patients with advanced solid tumors. An exploration cohort has been added to determine the safety using Q4W dosing.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Evaluate MEDI4736 given every 2 weeks
medi4736 Durvalumab
MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.
(Experimental)
Evaluate MEDI4736 given every 3 weeks
medi4736 Durvalumab
MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.
(Experimental)
At least 16 different types of solid tumors will be evaluated in the expansion phase
medi4736 Durvalumab
MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.
(Experimental)
Evaluate MEDI4736 given every 4 weeks
medi4736 Durvalumab
MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Primary Outcomes

Measure
Number of participants experiencing dose-limiting toxicities, adverse events (AEs), serious adverse events (SAEs).
time frame: 90 days after the last dose of MEDI4736
Anti-tumor efficacy (dose expansion subjects)
time frame: Until end of study

Secondary Outcomes

Measure
Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736.
time frame: Up to 90 days after the last dose of MEDI4736
Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).
time frame: Up to 6 months after the last dose of MEDI4736.
Objective response rate (ORR)
time frame: Until end of study
Disease control rate (DCR)
time frame: Until end of study
Duration of response (DR)
time frame: Until end of study
Progression-free survival (PFS)
time frame: Until end of study
Overall survival (OS)
time frame: From first dose of study drug until death or up to 2 years

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

Inclusion Criteria: - Age 18 or older. - In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists. - In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, subjects must have failed, be intolerant to, be ineligible for, or have refused - 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 sample (dose-expansion only) Exclusion Criteria: - Any prior Grade ≥ 3 irAE while receiving immunotherapy - Prior exposure to any anti-PD-1 or anti-PD-L1 antibody - Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. - Prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors. - Active or prior documented autoimmune disease within the past 2 years - History of primary immunodeficiency - History of organ transplant that requires use of immunosuppressives - Symptomatic or untreated central nervous system (CNS) metastases requiring concurrent treatment - Other invasive malignancy within 2 years - Women who are pregnant or lactating - Uncontrolled intercurrent illness - Known history of tuberculosis - Known to be human immunodeficiency virus (HIV) positive - Known to be Hepatitis B or C positive (except HCC patients)

Additional Information

Official title A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects With Advanced Solid Tumors
Description A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1)) will evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4736 in adult patients with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by MedImmune LLC.