Evaluation of Safety, Tolerability, PK & PD of Intravenous VX15/2503 in Patients With Advanced Solid Tumors
The purpose of this study is to evaluate the safety and tolerability of IV administration of VX15/2503 in patients with advanced solid tumors. The escalation part of the study will determine the maximum tolerated dose (MTD).
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Intravenous Infusion of VX15/2503 in Adult Patients With Advanced Solid Tumors|
- Safety/tolerability as measured by number of patients with adverse events [ Time Frame: Up to 18 months ] [ Designated as safety issue: Yes ]Subject incidence of treatment-emergent adverse events
- Maximum tolerated dose as measured by frequency of dose limiting toxicities [ Time Frame: Four (4) weeks after first dose ] [ Designated as safety issue: Yes ]
- Peak plasma concentration (Cmax) of VX15/2503 [ Time Frame: Four (4) hours after start of infusion ] [ Designated as safety issue: No ]
- Area under the plasma concentration versus time curve (AUC) of VX15/2503 [ Time Frame: Up to seven (7) days after first dose ] [ Designated as safety issue: No ]
- Half-life of VX15/2503 [ Time Frame: Up to 14 days after first dose ] [ Designated as safety issue: No ]
- SEMA4D T cell percent saturation of VX15/2503 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
- Number of patients who develop anti-drug antibody [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
- Overall response rate (ORR) using RECIST 1.1 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
- Progression-free survival (PFS) using RECIST 1.1 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
|Study Start Date:||January 2011|
|Estimated Study Completion Date:||October 2014|
|Estimated Primary Completion Date:||June 2014 (Final data collection date for primary outcome measure)|
VX15/2503 monoclonal antibody at a concentration of 0.3 mg/kg - 20 mg/kg to be administered intravenously on a weekly dosing cycle.
Dose escalation will begin at low doses and will gradually increase in each future cohort. The current trial design provides for 7 study cohorts with a 20 mg/kg expansion phase.
VX15/2503-01 is a dose-escalation, open label study to evaluate the safety and tolerability of IV administered VX15/2503 in patients with advanced solid tumors. This will be accomplished by using a dose escalation procedure starting at low doses of VX15/2503 and will continue based on predefined parameters until the maximum tolerated dose is identified.
The study drug, VX15/2503, is a monoclonal antibody that binds to the semaphorin 4D (SEMA4D; CD100) antigen. Semaphorins have been shown to play an important role in certain physiological processes such as vascular growth, tumor progression and immune cell regulation. Experimental evidence suggests that SEMA4D has two mechanisms of action that result in angiogenesis and tumor proliferation and invasion. Antibody neutralization of SEMA4D thus may represent a new therapeutic strategy for cancer treatment.
|United States, Arizona|
|Virginia G. Piper Cancer Center at Scottsdale Healthcare|
|Scottsdale, Arizona, United States, 85258|
|United States, Texas|
|South Texas Accelerated Research Therapeutics, LLC|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Amita Patnaik, MD||South Texas Accelerated Research Therapeutics, LLC|
|Principal Investigator:||Ramesh K Ramanathan, MD||TGen Clinical Research Service at Scottsdale Healthcare|