Clinical Trials/NCT02978482

NCT02978482

Completed

Phase 1

A Phase 1/2 Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Durvalumab (MEDI4736) in Combination With Tremelimumab in Chinese Patients With Advanced Malignancies

AstraZeneca1 site in 1 country26 target enrollmentDecember 1, 2016

ConditionsAdvanced Malignancy

Interventionsdurvalumab tremelimumab + durvalumab

Drugsdurvalumab tremelimumab + durvalumab

Overview

Phase: Phase 1
Intervention: durvalumab
Conditions: Advanced Malignancy
Sponsor: AstraZeneca
Enrollment: 26
Locations: 1
Primary Endpoint: Area under the plasma drug concentration-time curve from time zero to Day 28 post-dose (AUC 0-28)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

A Phase 1/2 Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of Durvalumab (MEDI4736) in combination with tremelimumab in Chinese Patients with Advanced Malignancies

Registry

clinicaltrials.gov

Start Date

December 1, 2016

End Date

November 26, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

AstraZeneca

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Provision of informed consent prior to any study specific procedures
•Male or female, aged at least 18 years
•For Phase 1 PK cohort:
•Patients with histologically or cytologically confirmed advanced and/or metastatic solid tumors other than HCC refractory or intolerable to existing standard of treatment
•For Phase 2 cohort:
•For nasopharyngeal carcinoma:
•Patients with histologically or cytologically confirmed nasopharyngeal carcinoma must have locally advanced or metastatic disease progressed on or after at least 1 chemotherapy regimen with or without radiotherapy.
•ONLY FOR PHASE 2 PORTION: mandatory tumor sample
•No prior exposure to immune-mediated therapy including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
•Life expectancy ≥12 weeks at Day 1

Exclusion Criteria

•Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. Note: Local treatment of isolated lesions for palliative intent is acceptable (eg, local surgery or radiotherapy).
•Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment. If sufficient washout time has not occurred due to the schedule or PK properties of an agent, a longer washout period will be required, as agreed upon by AstraZeneca and the Investigator.
•Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug.
•Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
•History of allogenic organ transplantation
•Any unresolved toxicity National Cancer Institute (NCI) CTCAE Version 4.03 Grade ≥2 from previous anticancer therapy
•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc).
•Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent
•History of another primary malignancy
•History of leptomeningeal carcinomatosis

Arms & Interventions

durvalumab

durvalumab alone

Intervention: durvalumab

durvalumab+tremelimumab

durvalumab plus tremelimumab

Intervention: tremelimumab + durvalumab

Outcomes

Primary Outcomes

Area under the plasma drug concentration-time curve from time zero to Day 28 post-dose (AUC 0-28)

Time Frame: approximately 6 months after the last evaluable patient is first dosed in phase 1 portion

Only for phase 1 portion of the study

Maximum plasma concentration (Cmax)

Time Frame: approximately 6 months after the last evaluable patient in Phase 1 portion is first dosed

Only for phase 1 portion of the study

Trough plasma concentration (Ctrough)

Time Frame: approximately 6 months after the last evaluable patient is first dosed in phase 1 portion

Only for phase 1 portion of the study

Adverse event

Time Frame: Approximately 12 months after the last evaluable patient from Ph 1 is 1st dosed or the last patient has withdrawn from study or the study discontinued by Sponsor

Objective response rate (ORR)

Time Frame: Approximately 12 months after the last evaluable patient is dosed, or the last patient has withdrawn from the study or the study is discontinued by the sponsor.

Only for phase 2 portion of the study (Phase 2 part withdrawn without initiation)

Secondary Outcomes

Anti-drug antibody (ADA)(approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor)
Complete response/Partial response/Stable disease/Progressive disease(approximately 6 months after the last evaluable patient is first dosed in phase 1 portion)
Overall survival (OS)(approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor)
Anti-drug antibody neutralizing antibodies (ADA nAB)(approximately 12 months after the last evaluable patient is first dosed, or the last patient has withdrawn from the study, or the study is discontinued by the Sponsor)