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

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

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 Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: VX15/2503

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.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Virginia G. Piper Cancer Center at Scottsdale Healthcare
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VX15/2503; VX15/2503 monoclonal antibody at a concentration of 0.3 mg/kg - 20 mg/kg to be administered intravenously on a weekly dosing cycle.	Drug: VX15/2503; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/tolerability as measured by number of patients with adverse events	Subject incidence of treatment-emergent adverse events	Up to 18 months
Maximum tolerated dose as measured by frequency of dose limiting toxicities		Four (4) weeks after first dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak plasma concentration (Cmax) of VX15/2503	Four (4) hours after start of infusion
Area under the plasma concentration versus time curve (AUC) of VX15/2503	Up to seven (7) days after first dose
Half-life of VX15/2503	Up to 14 days after first dose

Other Outcome Measures

Outcome Measure	Time Frame
SEMA4D T cell percent saturation of VX15/2503	Up to 18 months
Number of patients who develop anti-drug antibody	Up to 18 months
Overall response rate (ORR) using RECIST 1.1	Up to 18 months
Progression-free survival (PFS) using RECIST 1.1	Up to 18 months

Collaborators and Investigators

• Sponsor: Vaccinex Inc.
• Collaborators: PPD
• Investigators: Principal Investigator: Amita Patnaik, MD, South Texas Accelerated Research Therapeutics, LLC; Principal Investigator: Ramesh K Ramanathan, MD, TGEN Clinical Research Service at Scottsdale Healthcare

Publications and helpful links

General Publications

• Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 4, 2011
• First Submitted That Met QC Criteria: March 9, 2011
• First Posted (Estimate): March 11, 2011

Study Record Updates

• Last Update Posted (Estimate): August 13, 2014
• Last Update Submitted That Met QC Criteria: August 11, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; advanced solid tumors; pharmacodynamics; VX15/2503; Semaphorin 4D; SEMA4D; CD100
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: VX15/2503-01 v.9