MEDI4736 Alone and in Combination With Tremelimumab or AZD9150 in Adult Subjects With Relapsed/Refractory DLBCL (D4190C00023)

Phase 1

Completed

• Conditions: Diffuse Large B-Cell Lymphoma
• Interventions: Drug: MEDI4736; Drug: AZD9150; Drug: tremelimumab

• Registration Number: NCT02549651
• Lead Sponsor: MedImmune LLC

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and efficacy of MEDI4736 (durvalumab) alone and in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory dIffuse large B-cell lymphoma.

Detailed Description

This is a multicenter, open-label, dose-escalation and dose-expansion study of MEDI4736 (durvalumab) as monotherapy or in combination with either tremelimumab or AZD9150. The objectives are to describe any dose-limiting toxicities, determine the maximum tolerated dose, and evaluate the safety, tolerability, efficacy, immunogenicity, pharmacokinetics, and pharmacodynamics of MEDI4736 as monotherapy or in combination with either tremelimumab or AZD9150 in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.

Study Timeline

• Study First Submitted: 2015-08-27
• Study First Submitted QC: 2015-09-11
• Study First Posted: 2015-09-15
• Study Start: 2016-07-13
• Status Verified: 2019-02
• Primary Completion: 2019-02-04
• Study Completion: 2019-02-04
• Last Update Submitted: 2019-02-26
• Last Update Posted: 2019-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

1. Age ≥ 18 years
2. Subjects with histologically confirmed relapsed or refractory DLBCL who have received at least 1 prior rituximab containing chemotherapy regimen but no more than 5 prior lines of therapy
3. Eastern Cooperative Group (ECOG) performance status of 0 or 1
4. Measurable disease by International Working Group (IWG) response criteria for lymphoma
5. Adequate organ and marrow function

Exclusion Criteria

1. Previous immune-mediated therapy

2. Subjects with prior ASCT or allogenic HCT. Subjects ineligible for available curative options after failing ASCT and have met the hematologic criteria are eligible to participate in this study. Subjects with prior allogenic HCT will be excluded.

3. Documented current central nervous system involvement

4. Active or prior documented autoimmune or inflammatory disease within 3 years, with some exceptions 4. Concurrent or prior conventional or investigational anticancer therapy, within 28 days prior to the first dose of study medication(s)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MEDI4736	MEDI4736	-
MEDI4736 and tremelimumab	MEDI4736	-
MEDI4736 and AZD9150	MEDI4736	-
MEDI4736 and AZD9150	AZD9150	-
MEDI4736 and tremelimumab	tremelimumab	-

Primary Outcome Measures

Name	Time	Method
Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events	Screening through 90 days after the last dose of study medication
Number of subjects experiencing dose-limiting toxicities	First dose of study medications through 28 days after the administration of MEDI4736 or MEDI4736 and tremelimumab, 35 days after administration of MEDI4736 and AZD9150	Changes from baseline in laboratory parameters, vital signs, and ECGs

Secondary Outcome Measures

Name	Time	Method
Number of subjects who develop anti-drug antibodies (ADA)	Screening through 90 days after last dose of study medication
Time to Response	Screening though 3 years after the last subject receives the first dose of study medication
Duration of Response	Screening though 3 years after the last subject receives the first dose of study medication
MEDI4736 Maximum Plasma Concentration (Cmax)	Measured at defined study visits from time of first dose through end of treatment
Progression Free survival	Screening though 3 years after the last subject receives the first dose of study medication
Time to progression	Screening though 3 years after the last subject receives the first dose of study medication
Event free survival	Screening though 3 years after the last subject receives the first dose of study medication
Overall survival	Screening though 3 years after the last subject receives the first dose of study medication
Tremelimumab Maximum Plasma Concentration (Cmax)	Measured at defined study visits from time of first dose through end of treatment
AZD9150 Maximum Plasma Concentration (Cmax)	Measured at defined study visits from time of first dose through end of treatment
MEDI4736 Minimum Plasma Concentration (Cmin)	Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Minimum Plasma Concentration (Cmin)	Measured at defined study visits from time of first dose through end of treatment
AZD9150 Minimum Plasma Concentration (Cmin)	Measured at defined study visits from time of first dose through end of treatment
Individual MEDI4736 Concentrations	Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual tremelimumab Concentrations	Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual AZD9150 Concentrations	Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Change from baseline of STAT3 RNA (signal transducer and activator of transcription)	Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
Baseline PD-L1 protein expression within the tumor	Measured on tumor samples provided at screening

Trial Locations

Locations (1)

Research Site; 🇬🇧 Leicester, United Kingdom