Clinical trial NCT01313065: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: VX15/2503
Semaphorin 4D
SEMA4D
CD100
safety
tolerability
pharmacokinetics
pharmacodynamics
advanced solid tumors
Lead sponsor: Vaccinex Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2011-03-11
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Safety/tolerability as measured by number of patients with adverse events
timeFrame: Up to 18 months
measure: Maximum tolerated dose as measured by frequency of dose limiting toxicities
timeFrame: Four (4) weeks after first dose
Secondary outcomes:
measure: Peak plasma concentration (Cmax) of VX15/2503
timeFrame: Four (4) hours after start of infusion
measure: Area under the plasma concentration versus time curve (AUC) of VX15/2503
timeFrame: Up to seven (7) days after first dose
measure: Half-life of VX15/2503
timeFrame: Up to 14 days after first dose
Other outcomes:
measure: SEMA4D T cell percent saturation of VX15/2503
timeFrame: Up to 18 months
measure: Number of patients who develop anti-drug antibody
timeFrame: Up to 18 months
measure: Overall response rate (ORR) using RECIST 1.1
timeFrame: Up to 18 months
measure: Progression-free survival (PFS) using RECIST 1.1
timeFrame: Up to 18 months
Locations:
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare
state: Arizona
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
Study officials:
affiliation: South Texas Accelerated Research Therapeutics, LLC
name: Amita Patnaik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: TGen Clinical Research Service at Scottsdale Healthcare
name: Ramesh K Ramanathan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Worzfeld T, Offermanns S. Semaphorins and plexins as therapeutic targets. Nat Rev Drug Discov. 2014 Aug;13(8):603-21. doi: 10.1038/nrd4337.