Clinical trial NCT02549651: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: DLBCL
MEDI4736
durvalumab
tremelimumab
AZD9150
anti-PD-L1
anti-CTLA-4
immunotherapy
IMTC
STAT3
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2015-09-15
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of subjects reporting adverse events and number (percentage) of subjects reporting serious adverse events
timeFrame: Screening through 90 days after the last dose of study medication
measure: Number of subjects experiencing dose-limiting toxicities
timeFrame: 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 outcomes:
measure: Number of subjects who develop anti-drug antibodies (ADA)
timeFrame: Screening through 90 days after last dose of study medication
measure: Time to Response
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: Duration of Response
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: Progression Free survival
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: Time to progression
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: Event free survival
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: Overall survival
timeFrame: Screening though 3 years after the last subject receives the first dose of study medication
measure: MEDI4736 Maximum Plasma Concentration (Cmax)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: Tremelimumab Maximum Plasma Concentration (Cmax)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: AZD9150 Maximum Plasma Concentration (Cmax)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: MEDI4736 Minimum Plasma Concentration (Cmin)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: Tremelimumab Minimum Plasma Concentration (Cmin)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: AZD9150 Minimum Plasma Concentration (Cmin)
timeFrame: Measured at defined study visits from time of first dose through end of treatment
measure: Individual MEDI4736 Concentrations
timeFrame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
measure: Individual tremelimumab Concentrations
timeFrame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
measure: Individual AZD9150 Concentrations
timeFrame: Measured at defined study visits from time of first dose through 90 days after the end of treatment (approximately 15 months)
measure: Change from baseline of STAT3 RNA (signal transducer and activator of transcription)
timeFrame: Measured at defined study visits from time of first dose through 90 days after last dose (approximately 15 months)
measure: Baseline PD-L1 protein expression within the tumor
timeFrame: Measured on tumor samples provided at screening
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Research Site
state: California
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Marseille
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Dublin 8
country: Ireland
facility: Research Site
city: Galway
country: Ireland
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: