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Evaluation of Safety, Tolerability, PK & PD of Intravenous VX15/2503 in Patients With Advanced Solid Tumors

Phase 1
Completed
Conditions
Solid Tumors
Interventions
Registration Number
NCT01313065
Lead Sponsor
Vaccinex Inc.
Brief Summary

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).

Detailed Description

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
42
Inclusion Criteria
  • Patients 18 yrs or older with confirmed histological or cytological advanced solid tumors, relapsed or refractory to standard treatment for which no curative therapy is available; patients must demonstrate progressive disease prior to entry
  • Has measurable disease as defined by RECIST1.1
  • Life expectancy of at least 3 months (per investigator assessment)
  • ECOG performance status of 0-2
  • Adequate bone marrow, renal and liver function
  • Recovered from any significant prior toxicity of previous anti-neoplastic therapy
  • For patients of reproductive potential, is willing to use a medically acceptable form of contraception throughout the study period and for at least 4 weeks after the last dose of VX15/2503
  • Expansion cohort - patients in this cohort must have one of the following characteristics:
  • A diagnosis of a pancreatic neuroendocrine tumor OR
  • A diagnosis of a soft tissue sarcoma OR
  • A diagnosis of a bone metastasis OR
  • A diagnosis of advanced solid tumor AND a T cell count of at least 1500 cells/uL OR a B cell count of at least 250 cells/uL at screening

Main

Exclusion Criteria
  • Treatment with anti-neoplastic agents (chemotherapy, immunotherapy, radiotherapy or endocrine therapy) within 3 weeks prior to start of study treatment
  • Treatment with an investigational agent within 4 weeks prior to start of study treatment
  • Is on concurrent anti-neoplastic therapy with the exception of continuing luteinizing hormone-releasing hormone agonist/antagonist therapy for patients with castrate-resistant prostate cancer
  • Treatment with oral or parenteral corticosteroids in excess of 10mg/day of prednisolone or equivalent for more than 5 days within 4 weeks prior to start of study treatment or a requirement for systemic immunosuppressive therapy for any reason
  • Untreated brain Mets or CNS tumor involvement
  • Any other intercurrent illness or condition which could impact patient compliance or ability to complete the study
  • Sensitivity to VX15/2503 or the ingredients or excipients of VX15/2503
  • Pregnant or breast-feeding women (women of child-bearing potential must have negative serum pregnancy test within 3 days prior to receiving the first dose of VX15/2503)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
VX15/2503VX15/2503VX15/2503 monoclonal antibody at a concentration of 0.3 mg/kg - 20 mg/kg to be administered intravenously on a weekly dosing cycle.
Primary Outcome Measures
NameTimeMethod
Safety/tolerability as measured by number of patients with adverse eventsUp to 18 months

Subject incidence of treatment-emergent adverse events

Maximum tolerated dose as measured by frequency of dose limiting toxicitiesFour (4) weeks after first dose
Secondary Outcome Measures
NameTimeMethod
Peak plasma concentration (Cmax) of VX15/2503Four (4) hours after start of infusion
Area under the plasma concentration versus time curve (AUC) of VX15/2503Up to seven (7) days after first dose
Half-life of VX15/2503Up to 14 days after first dose

Trial Locations

Locations (2)

South Texas Accelerated Research Therapeutics, LLC

🇺🇸

San Antonio, Texas, United States

Virginia G. Piper Cancer Center at Scottsdale Healthcare

🇺🇸

Scottsdale, Arizona, United States

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