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

Diffuse Large B-Cell Lymphoma Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02549651
• Other study ID #: D4190C00023
• Status: Completed
• Phase: Phase 1
• Start date: July 13, 2016
• Est. completion date: February 4, 2019

Study information

• Verified date: February 2019
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 4, 2019
• Est. primary completion date: February 4, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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)

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• MEDI4736
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
• tremelimumab
Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
• AZD9150
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion

Locations

Country	Name	City	State
France	Research Site	Marseille
France	Research Site	Villejuif
Ireland	Research Site	Dublin 8
Ireland	Research Site	Galway
United Kingdom	Research Site	Leicester
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Baltimore	Maryland
United States	Research Site	Charleston	South Carolina
United States	Research Site	Dallas	Texas
United States	Research Site	Durham	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	La Jolla	California
United States	Research Site	Milwaukee	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  France,  Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of subjects experiencing dose-limiting toxicities	Changes from baseline in laboratory parameters, vital signs, and ECGs	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	Number of subjects who develop anti-drug antibodies (ADA)		Screening through 90 days after last dose of study medication
Secondary	Time to Response		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	Duration of Response		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	Progression Free survival		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	Time to progression		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	Event free survival		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	Overall survival		Screening though 3 years after the last subject receives the first dose of study medication
Secondary	MEDI4736 Maximum Plasma Concentration (Cmax)		Measured at defined study visits from time of first dose through end of treatment
Secondary	Tremelimumab Maximum Plasma Concentration (Cmax)		Measured at defined study visits from time of first dose through end of treatment
Secondary	AZD9150 Maximum Plasma Concentration (Cmax)		Measured at defined study visits from time of first dose through end of treatment
Secondary	MEDI4736 Minimum Plasma Concentration (Cmin)		Measured at defined study visits from time of first dose through end of treatment
Secondary	Tremelimumab Minimum Plasma Concentration (Cmin)		Measured at defined study visits from time of first dose through end of treatment
Secondary	AZD9150 Minimum Plasma Concentration (Cmin)		Measured at defined study visits from time of first dose through end of treatment
Secondary	Individual MEDI4736 Concentrations		Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Secondary	Individual tremelimumab Concentrations		Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Secondary	Individual AZD9150 Concentrations		Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Secondary	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)
Secondary	Baseline PD-L1 protein expression within the tumor		Measured on tumor samples provided at screening