Olvi-Vec Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer

Phase 1b & 2 Study With Olvi-Vec Oncolytic Immunotherapy in Patients With Recurrent or Refractory Ovarian Cancer (VIRO-15)

The purpose of this study is to determine if Olvi-Vec oncolytic immunotherapy is well tolerated with anti-tumor activity in patients diagnosed with recurrent or refractory ovarian cancer and peritoneal carcinomatosis.

Ovarian cancer (OC) remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemo-resistance and remarkable heterogeneity. There is an unmet medical need to develop new therapy modalities. In preclinical studies, Olvi-Vec, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors, including ovarian cancer. Olvi-Vec 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. Olvi-Vec treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of Olvi-Vec to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and favorable anti-tumor immune response have been observed. Evidences of anti-tumor efficacy and clinical benefits have also been documented.

Inclusion Criteria:

• Signed, written informed consent.
• High-grade serous (including Malignant Mixed Mullerian Tumor (MMMT) with metastasis that contains high grade epithelial carcinoma), endometrioid, or clear-cell ovarian cancer which includes: (1) platinum-resistant (recurrence or progression in < 6 months) or (2) platinum-refractory (progression while on platinum-based therapy); patient must have failed either at least 2 consecutive therapies or are not eligible for additional cytotoxic therapies (exception is Phase 2 receiving chemotherapy with/without bevacizumab).
• Intermediate platinum-sensitive patients (recurrence of disease 6 to 12 months from last platinum compound treatment): Recurrent ovarian carcinoma with at least four prior individual treatment regimens including at least two separate platinum-based therapies with recurrence from the last platinum-based regimen less than 12 months, who are unwilling or unable to undergo additional platinum-based cytotoxic therapy (this sub-population is not applicable for Phase 2 receiving chemotherapy with/without bevacizumab).
• Performance status ECOG is at 0 or 1, and life expectancy of 6 months
• Has either measurable disease in the peritoneal cavity as defined by RECIST 1.1 (Phase 1b & 2) or has non-measurable disease in the peritoneal cavity (Phase 1b) and can be confirmed by laparoscopy and/or elevated CA-125. Patients who have non-measurable disease that is not identifiable by PET/PET-CT scan, but who have elevated CA-125, and/or ascites, with visible disease confirmed by laparoscopy are also eligible.
• Able to undergo IP injection.
• Adequate renal, hepatic, bone marrow and immune functions.
• Baseline tumor biopsy is required.
• Documented progressive disease status at baseline (Phase 2).

Exclusion Criteria:

• Tumors of mucinous subtypes, or non-epithelial ovarian cancers (e.g., Brenner tumors, Sex-cord tumors).
• Unresolved bowel obstruction.
• Known central nervous system (CNS) metastasis.
• Known seropositivity for HIV or active hepatitis infection.
• History of thromboembolic event within the last 3 months.
• Pregnant or breast-feeding women.
• Smallpox vaccination within 1 year of study treatment.
• Clinically significant cardiac disease.
• Received prior gene therapy or therapy with cytolytic virus of any type.
• Receiving concurrent antiviral agent active against vaccinia virus.
• Have known allergy to ovalbumin or other egg products.
• Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or unhealed skin wounds or ulcers) as assessed by the Investigator.
• Symptomatic malignant ascites and non-manageable pleural effusion.
• Known hypersensitivity to bevacizumab, uncontrolled hypertension, history of stroke, or clinical findings suggestive of excessive risk for GL perforation (uncontrolled peptic ulcer disease, partial small bowel obstruction, etc.) that would make risks of bevacizumab unacceptable in the opinion of the investigator.