GL-ONC1 Administered Intravenously Prior to Surgery to Patients With Solid Organ Cancers

An Open Label, Non-randomized Phase 1b Study to Investigate the Safety and Effect of the Oncolytic Virus GL-ONC1 Administered Intravenously Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery for Curative-Intent or Palliative Resection

The purpose of this study is to evaluate the safety of the investigational product GL-ONC1. GL-ONC1, a vaccinia virus, has been genetically modified for use as a potential anti-cancer drug to destroy cancer cells. Vaccinia virus has been used successfully in the past as smallpox vaccine in millions of people worldwide.

This is an open-label, non-randomized Phase 1b dose escalation study evaluating the safety and effect of the oncolytic virus GL-ONC1 administered intravenously, with or without eculizumab, prior to surgery in patients with advanced solid organ tumors.

GL-ONC1 is a genetically engineered oncolytic vaccinia virus, which disrupts nonessential genes and expression of the foreign gene expression. Evidence suggest that GL-ONC1 is able to infect tumor tissue and kill tumor cells.

The goals of this study are to evaluate the safety of GL-ONC1 and to assess the pharmacokinetics and pharmacodynamics profile of GL-ONC1 in vivo.

Inclusion Criteria:

• Histologically-proven diagnosis of advanced (AJCC, 7th Edition: stage III or IV) or aggressive solid organ cancer.
• Patients must provide written consent for a core needle biopsy sample of tumor tissue (primary or metastatic).
• Have evidence of measurable disease (according to RECIST Version 1.1: http:// www.recist.com).
• Have an ECOG Performance Score of 0 to 2.
• Have a life expectancy of at least 3 months.
• Have adequate organ and marrow function
• Negative serum pregnancy test for females of childbearing potential.
• Have negative test result for HIV and Hepatitis B or C testing.
• Have baseline anti-vaccinia antibody titer < 10.

Exclusion Criteria:

• Current or anticipated use of other investigational agents or marketed anticancer agent while on study (from the time of enrollment through the time of surgery).
• Patients who have received chemotherapy or radiotherapy within 4 weeks prior to entering the study.
• Small pox vaccination for 4 weeks before study therapy and during study treatment.
• Have received prior gene therapy or therapy with cytolytic virus of any type.
• Have clinically significant cardiac disease
• Oxygen saturation <90% measured by pulse oximetry at rest.
• Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study.
• Have known allergy to ovalbumin or other egg products.
• Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers)
• Have a history of allergy to iodinated contrast media.
• Patients with known brain metastases
• Pregnant or nursing