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

• ClinicalTrials.gov Identifier: NCT01313065
• Recruitment Status: Completed
• First Posted: March 11, 2011
• Last Update Posted: August 13, 2014
• Sponsor: Vaccinex Inc.
• Collaborator: PPD
• Information provided by (Responsible Party): Vaccinex Inc.

Tracking Information

• First Submitted Date: March 4, 2011
• First Posted Date: March 11, 2011
• Last Update Posted Date: August 13, 2014
• Study Start Date: January 2011
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 19, 2013)

• Safety/tolerability as measured by number of patients with adverse events [ Time Frame: Up to 18 months ]
  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 ]

Original Primary Outcome Measures (submitted: March 9, 2011)

• Safety/tolerability as measured by number of patients with adverse events [ Time Frame: Up to one (1) year ]
  Subject incidence of treatment-emergent adverse events
• Maximum tolerated dose as measured by frequency of dose limiting toxicities [ Time Frame: Six (6) weeks ]

Current Secondary Outcome Measures (submitted: June 19, 2013)

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

Original Secondary Outcome Measures (submitted: March 9, 2011)

• Pharmacokinetics as measured by Cmax, CL, Vd, Vss and AUCs [ Time Frame: 0,1,4,8,24,48,96,148,240 and 336 hours after start of infusion ]
• Pharmacodynamics as measured by SEMA4D T cell saturation [ Time Frame: 0,1,4,8,24,48,96,148, 240 and 336 hours after start of infusion ]
• Immunogenicity as measured by number of patients who develop anti-drug antibody [ Time Frame: Up to one (1) year ]

Current Other Pre-specified Outcome Measures (submitted: June 19, 2013)

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

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Safety, Tolerability, PK & PD of Intravenous VX15/2503 in Patients With Advanced Solid Tumors
• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumors

Intervention

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.

Study Arms

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.

Intervention: Drug: VX15/2503

• 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. Review.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 11, 2014): 42
• Original Estimated Enrollment (submitted: March 9, 2011): 54
• Actual Study Completion Date: June 2014
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01313065
• Other Study ID Numbers: VX15/2503-01 v.9
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vaccinex Inc.
• Original Responsible Party: John H. Parker, Ph.D., Senior Director, Regulatory Affairs and Quality Systems, Vaccinex, Inc.
• Current Study Sponsor: Vaccinex Inc.
• Original Study Sponsor: Same as current
• 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

• PRS Account: Vaccinex Inc.
• Verification Date: August 2014