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

Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01313065
• Other study ID #: VX15/2503-01 v.9
• Status: Completed
• Phase: Phase 1
• First received: March 4, 2011
• Last updated: August 11, 2014
• Start date: January 2011
• Est. completion date: June 2014

Study information

• Verified date: August 2014
• Source: Vaccinex Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• 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.

Locations

Country	Name	City	State
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare	Scottsdale	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Vaccinex Inc.	PPD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	SEMA4D T cell percent saturation of VX15/2503		Up to 18 months	No
Other	Number of patients who develop anti-drug antibody		Up to 18 months	No
Other	Overall response rate (ORR) using RECIST 1.1		Up to 18 months	No
Other	Progression-free survival (PFS) using RECIST 1.1		Up to 18 months	No
Primary	Safety/tolerability as measured by number of patients with adverse events	Subject incidence of treatment-emergent adverse events	Up to 18 months	Yes
Primary	Maximum tolerated dose as measured by frequency of dose limiting toxicities		Four (4) weeks after first dose	Yes
Secondary	Peak plasma concentration (Cmax) of VX15/2503		Four (4) hours after start of infusion	No
Secondary	Area under the plasma concentration versus time curve (AUC) of VX15/2503		Up to seven (7) days after first dose	No
Secondary	Half-life of VX15/2503		Up to 14 days after first dose	No