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

Sponsor

MedImmune LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02549651

Collaborator

(none)

Enrollment

Locations

Arms

30.8

Actual Duration (Months)

2.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-Cell Lymphoma	Drug: MEDI4736 Drug: tremelimumab Drug: AZD9150	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

32 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Jul 13, 2016

Actual Primary Completion Date :

Feb 4, 2019

Actual Study Completion Date :

Feb 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEDI4736	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Experimental: MEDI4736 and tremelimumab	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion Drug: tremelimumab Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
Experimental: MEDI4736 and AZD9150	Drug: MEDI4736 MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion Drug: AZD9150 AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion

Arm

Intervention/Treatment

Experimental: MEDI4736

Drug: MEDI4736

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

Experimental: MEDI4736 and tremelimumab

Drug: MEDI4736

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

Drug: tremelimumab

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

Experimental: MEDI4736 and AZD9150

Drug: MEDI4736

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

Drug: AZD9150

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

Outcome Measures

Primary Outcome Measures

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

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]
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]
MEDI4736 Maximum Plasma Concentration (Cmax) [Measured at defined study visits from time of first dose through end of treatment]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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
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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	La Jolla	California	United States	92093
2	Research Site	Baltimore	Maryland	United States	21201
3	Research Site	Albuquerque	New Mexico	United States	87131
4	Research Site	Durham	North Carolina	United States	27710
5	Research Site	Charleston	South Carolina	United States	29425
6	Research Site	Dallas	Texas	United States	75390
7	Research Site	Houston	Texas	United States	77030
8	Research Site	Milwaukee	Wisconsin	United States	53226
9	Research Site	Marseille		France	13273
10	Research Site	Villejuif		France	94805
11	Research Site	Dublin 8		Ireland
12	Research Site	Galway		Ireland
13	Research Site	Leicester		United Kingdom	LE1 5WW