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.
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
32
MEDI4736 is an anti-PD-L1 monoclonal antibody (MAb) administered via intravenous infusion
Tremelimumab is an anti-CTLA4 monoclonal antibody (MAb) administered via intravenous infusion
AZD9150 is an antisense oligonucleotide (ASO) administered via intravenous infusion
Research Site
La Jolla, California, United States
Research Site
Baltimore, Maryland, United States
Research Site
Albuquerque, New Mexico, United States
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
Number of subjects experiencing dose-limiting toxicities
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
Number of subjects who develop anti-drug antibodies (ADA)
Time frame: Screening through 90 days after last dose of study medication
Time to Response
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Duration of Response
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Progression Free survival
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Time to progression
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Event free survival
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
Overall survival
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Research Site
Durham, North Carolina, United States
Research Site
Charleston, South Carolina, United States
Research Site
Dallas, Texas, United States
Research Site
Houston, Texas, United States
Research Site
Milwaukee, Wisconsin, United States
Research Site
Marseille, France
Research Site
Villejuif, France
...and 3 more locations
Time frame: Screening though 3 years after the last subject receives the first dose of study medication
MEDI4736 Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Maximum Plasma Concentration (Cmax)
Time frame: Measured at defined study visits from time of first dose through end of treatment
MEDI4736 Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Tremelimumab Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
AZD9150 Minimum Plasma Concentration (Cmin)
Time frame: Measured at defined study visits from time of first dose through end of treatment
Individual MEDI4736 Concentrations
Time frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual tremelimumab Concentrations
Time frame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
Individual AZD9150 Concentrations
Time frame: 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)
Time frame: 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
Time frame: Measured on tumor samples provided at screening