A Phase 1b/2 Safety and Tolerability of MEDI6469 in Combination With Therapeutic Immune Agents or Monoclonal Antibodies

Advanced Solid Tumors Clinical Trial

— MEDI6469  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02205333
• Other study ID #: D4981C00001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: July 18, 2014
• Last updated: May 2, 2016
• Start date: August 2014
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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, or rituximab in subjects with either advanced solid tumors or diffuse large B-cell lymphoma (DLBCL). Tremelimumab and MEDI4736 will be tested with MEDI6469 in a set of subjects with advanced solid tumors while rituximab will be tested with MEDI6469 in subjects with DLBCL. MEDI6469 will be tested as monotherapy in subjects with advanced solid tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 99 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Aggression
• Aggressive B-cell Lymphomas
• Lymphoma, B-Cell

Intervention

Biological:
• MEDI6469/tremelimumab
MEDI6469 in combination with tremelimumab
• MEDI6469/MEDI4736
MEDI6469 in combination with MEDI4736
• MEDI6469/rituximab
MEDI6469 in combination with rituximab
• MEDI6469
MEDI6469 monotherapy

Locations

Country	Name	City	State
United States	Research Site	Chicago	Illinois
United States	Research Site	Detroit	Michigan
United States	Research Site	Hackensack	New Jersey
United States	Research Site	Houston	Texas
United States	Research Site	Huntersville	North Carolina
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Memphis	Tennessee
United States	Research Site	Portland	Oregon
United States	Research Site	Sacramento	California
United States	Research Site	Santa Monica	California
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Tampa	Florida
United States	Research Site	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	The primary endpoint is the MTD, defined as the highest dose within a cohort where no more than 1 out of 6 subjects experience dose-limiting toxicities (DLTs), or the highest protocol-defined dose for each agent in the absence of exceeding the MTD.	From Day 1 up to 28 days at each dose level.	Yes
Primary	Safety	The primary endpoints for safety assessment include the number of participants experiencing adverse events (AEs) and the number of participants experiencing serious adverse events (SAEs).	From the signing of an informed consent form (Day -28) until 90 days after the last dose of investigational products.	Yes
Secondary	Antitumor Activity	The endpoints for assessment of antitumor activity include objective response and disease control based on revised Response Evaluation Criteria in Solid Tumors (RECIST) criteria Version 1.1 for solid tumors or based on Cheson Criteria for DLBCL (Cheson et al, 2007), duration of response, progression-free survival, and overall survival.	Participant's disease status will be assessed from date of randomization until documentation of disease progression, death, end of study or withdrawal of consent. Assessments will be performed between study days 57-59 and then every 28 days.	No
Secondary	Pharmacokinetics (PK)	MEDI6469 concentrations in serum and peak plasma concentrations (Cmax).	Assessments will be performed between Day 1 and end of treatment visit. Specifically assessments will be performed at certain timepoints (dependent upon cohort) on Days 1, 2, 3, 4, 8, 15, 29, 31, 59 and then every 28 days until end of treatment visit.	No
Secondary	Pharmacokinetics (PK)	Area under the the plasma concentration versus time curve (AUC) of MEDI6469.	Assessments will be performed between Day 1 and end of treatment visit. Specifically assessments will be performed at certain timepoints (dependent upon cohort) on Days 1, 2, 3, 4, 8, 15, 29, 31, 59 and then every 28 days until end of treatment visit.	No
Secondary	Pharmacokinetics (PK)	Clearance and half-life of MEDI6469.	Assessments will be performed between Day 1 and end of treatment visit. Specifically assessments will be performed at certain timepoints (dependent upon cohort) on Days 1, 2, 3, 4, 8, 15, 29, 31, 59 and then every 28 days until end of treatment visit.	No
Secondary	Immunogenicity	The endpoints for assessment of immunogenicity of MEDI6469 include the number and percentage of subjects who develop detectable anti-drug antibodies.	Assessments will be performed between Day 1 and the end of treatment visit. Specifically assessments will be performed at certain timepoints (dependent upon cohort) on Days 1, 3, 8, 15, 29, 31, 59 and then every 28 days until the end of treatment visit.	Yes