Clinical trial NCT02205333: A Phase 1b/2 Safety and Tolerability Study of MEDI6469 in Combination With Therapeutic Immune Agents or Monoclonal Antibodies
Official title: A Phase 1b/2, Open-label Study to Evaluate the Safety and Tolerability of MEDI6469 in Combination With Immune Therapeutic Agents or Therapeutic Monoclonal Antibodies in Subjects With Selected Advanced Solid Tumors or Aggressive B-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Aggressive B-cell Lymphomas
Keywords: Advanced Solid tumors
Diffuse Large B-cell Lymphoma
programmed death 1
programmed dealth ligand 1
cytotoxic T-lymphocyte-associated antigen-4
OX40 ligand
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-07-31
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to determine the best dose of MEDI6469 that is safe and tolerable when given as monotherapy and in combination with tremelimumab, MEDI4736 (durvalumab), or rituximab in participants with either advanced solid tumors or diffuse large B-cell lymphoma (DLBCL). Tremelimumab and MEDI4736 (durvalumab) will be tested with MEDI6469 in a set of participants with advanced solid tumors while rituximab will be tested with MEDI6469 in participants with DLBCL. MEDI6469 will be tested as monotherapy in participants with advanced solid tumors.


Eligibility criteria: Inclusion Criteria:

* Adults \>/= 18 years old
* Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy or for which no standard therapy exists (Monotherapy and in Cohorts A and B)
* At least one lesion measurable by RECIST not previously irradiated (Monotherapy and in Cohorts A and B)
* Histologically confirmed DLBCL(Cohort C)
* Adequate organ and marrow function
* ECOG performance status of 0 or 1
* Willingness to provide consent for biopsy samples

Exclusion Criteria:

* Prior exposure to immunotherapy (either as a single agent or in combination) including but not limited to CD137 or OX40 agonists, anti-CTLA-4, anti-PD-1, or anti-PD-L1, anti-PD-L2 antibody or pathway-targeting agents
* History of organ transplant that requires use of immunosuppressives
* History of primary immunodeficiency or tuberculosis
* Active or prior documented autoimmune disease within the past 3 years
* Active or chronic viral hepatitis or history of any type of hepatitis within the last 6 months
* Major surgical procedure within 30 days prior to the first dose of investigational product or still recovering from prior surgery
* Women who are pregnant or lactating

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of MEDI6469
timeFrame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
measure: Number of Participants With DLTs
timeFrame: From the first dose of study treatment through 28 days after the first dose (up to 28 days)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
measure: Number of Participants With Treatment-emergent Serious Adverse Events
timeFrame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
measure: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
timeFrame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
measure: Number of Participants With Vital Signs and Physical Examination Abnormalities Reported as TEAEs
timeFrame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
measure: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
timeFrame: From study treatment administration (Day 1) to 90 days after the last dose of study treatment or early termination of study (up to 1 year)
Secondary outcomes:
measure: Best Overall Response (BOR)
timeFrame: From study entry until early termination (up to 1 year)
measure: Objective Response Rate (ORR)
timeFrame: From study entry until early termination (up to 1 year)
measure: Disease Control Rate
timeFrame: From study entry until early termination (up to 1 year)
measure: Duration of Response (DOR)
timeFrame: From Study entry until early termination (up to 1 year)
measure: Progression-free Survival (PFS)
timeFrame: From Study entry until early termination (up to 1 year)
measure: Overall Survival (OS)
timeFrame: From Study entry until early termination (up to 1 year)
measure: Maximum Observed Serum Concentration (Cmax)
timeFrame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment
measure: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
timeFrame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
measure: Systemic Clearance (CL)
timeFrame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
measure: Terminal Phase Elimination Half-Life (T1/2)
timeFrame: MEDI6469 monotherapy: Days 1, 2, 3, 8, 15, and 29; MEDI6469 + tremelimumab or durvalumab: Days 1, 2, 3, 4, 8, 15, 29, and end of treatment (up to 1 year); MEDI6469 + rituximab: Days 3, 4, 8, 15, 29, 31, 59, every 28 days thereafter, and end of treatment.
measure: Number of Participants Positive for Human Anti-mouse Antibodies (HAMA)
timeFrame: All treatment arms: Days 8, 15, 29, and end of treatment (up to 1 year). Additionally for MEDI6469 + rituximab arm: Days 3, 31, 59, and every 28 days thereafter until end of treatment (up to 1 year)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Sacramento
country: United States
facility: Research Site
state: California
city: Santa Monica
country: United States
facility: Research Site
state: California
city: Washington, D.C.
country: United States
facility: Research Site
state: District of Columbia
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: Huntersville
country: United States
facility: Research Site
state: North Carolina
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: MedImmune LLC
name: MedImmune, LLC
role: STUDY_DIRECTOR
References: