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

Primary Purpose

Diffuse Large B-Cell Lymphoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

MEDI4736

tremelimumab

AZD9150

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring DLBCL, MEDI4736, durvalumab, tremelimumab, AZD9150, anti-PD-L1, anti-CTLA-4, immunotherapy, IMTC, STAT3

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18 years
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
Eastern Cooperative Group (ECOG) performance status of 0 or 1
Measurable disease by International Working Group (IWG) response criteria for lymphoma
Adequate organ and marrow function

Exclusion Criteria:

Previous immune-mediated therapy
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.
Documented current central nervous system involvement

3. 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)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

MEDI4736

MEDI4736 and tremelimumab

MEDI4736 and AZD9150

Arm Description

Outcomes

Primary Outcome Measures

Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events

Number of subjects experiencing dose-limiting toxicities

Changes from baseline in laboratory parameters, vital signs, and ECGs

Secondary Outcome Measures

Number of subjects who develop anti-drug antibodies (ADA)

Time to Response

Duration of Response

Progression Free survival

Time to progression

Event free survival

Overall survival

MEDI4736 Maximum Plasma Concentration (Cmax)

Tremelimumab Maximum Plasma Concentration (Cmax)

AZD9150 Maximum Plasma Concentration (Cmax)

MEDI4736 Minimum Plasma Concentration (Cmin)

Tremelimumab Minimum Plasma Concentration (Cmin)

AZD9150 Minimum Plasma Concentration (Cmin)

Individual MEDI4736 Concentrations

Individual tremelimumab Concentrations

Individual AZD9150 Concentrations

Change from baseline of STAT3 RNA (signal transducer and activator of transcription)

Baseline PD-L1 protein expression within the tumor

Full Information

NCT ID

NCT02549651

First Posted

August 27, 2015

Last Updated

February 26, 2019

Sponsor

MedImmune LLC

1. Study Identification

Unique Protocol Identification Number

NCT02549651

Brief Title

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

Official Title

A Phase 1b Study to Evaluate the Safety and Efficacy of MEDI4736 as Monotherapy and in Combination With Tremelimumab or AZD9150 in Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Completed

Study Start Date

July 13, 2016 (Actual)

Primary Completion Date

February 4, 2019 (Actual)

Study Completion Date

February 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

MedImmune LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diffuse Large B-Cell Lymphoma

Keywords

DLBCL, MEDI4736, durvalumab, tremelimumab, AZD9150, anti-PD-L1, anti-CTLA-4, immunotherapy, IMTC, STAT3

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

32 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MEDI4736

Arm Type

Experimental

Arm Title

MEDI4736 and tremelimumab

Arm Type

Experimental

Arm Title

MEDI4736 and AZD9150

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

MEDI4736

Intervention Description

MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion

Intervention Type

Drug

Intervention Name(s)

tremelimumab

Intervention Description

Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion

Intervention Type

Drug

Intervention Name(s)

AZD9150

Intervention Description

AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion

Primary Outcome Measure Information:

Title

Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events

Time Frame

Screening through 90 days after the last dose of study medication

Title

Number of subjects experiencing dose-limiting toxicities

Description

Changes from baseline in laboratory parameters, vital signs, and ECGs

Time Frame

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

Secondary Outcome Measure Information:

Title

Number of subjects who develop anti-drug antibodies (ADA)

Time Frame

Screening through 90 days after last dose of study medication

Title

Time to Response

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

Duration of Response

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

Progression Free survival

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

Time to progression

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

Event free survival

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

Overall survival

Time Frame

Screening though 3 years after the last subject receives the first dose of study medication

Title

MEDI4736 Maximum Plasma Concentration (Cmax)

Time Frame