Primary Outcome Measures
- Number of participants with treatment-related adverse events as defined by CTCAE v4.03. [ Time Frame: 2.5 years ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures
- The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen. [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
- The maximum concentration (Cmax) of GL-ONC1 in blood after administration [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
- Level of anti-vaccinia neutralizing antibodies in serum [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
- Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
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 has been investigated in early stage clinical trials in the United States and Europe via systemic delivery as monotherapy and in combination with other therapies, and via regional delivery as monotherapy. GL-ONC1 treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of GL-ONC1 to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and elevation of serum markers linking to a favorable antitumor immune response have been observed.
Eculizumab is a monoclonal antibody designed to inhibit the activity of a protein called complement which is part of the body’s innate immune system. Evidence from laboratory tests suggest eculizumab may allow GL-ONC1 to stay in the body longer before being cleared by the immune system.
The goals of this study are to evaluate the safety of concurrent systemic administration of eculizumab and 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).
- 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