Recombinant Vaccinia Virus Administered Intravenously in Patients With Metastatic, Refractory Colorectal Carcinoma

A Phase 1/2a Dose-escalation Study of JX 594 Administered by Multiple Intravenous (IV) Infusions Alone and in Combination With Irinotecan in Patients With Metastatic, Refractory Colorectal Carcinoma.

The purpose of this study is to evaluate the safety, tolerability, and efficacy of JX-594 (Pexa-Vec) administered intravenously either alone or in combination with Irinotecan in colorectal carcinoma patients who are refractory to or intolerant to standard therapy.

This was a Phase 1/2a, open-label, dose-escalation study in patients with advanced colorectal cancer (CRC)

Inclusion Criteria:

• Histologically-confirmed, advanced metastatic colorectal cancer failed treatment with fluoropyrimidine (fluoruracil or capecitabine) and oxaliplatin based therapies or had contradictions to treatment with these drugs as determined by the investigator
• Failed treatment with irinotecan
• Kras mutant tumor or Kras wild-type having failed cetuximab (Erbitux) or panitumumab (Vectibix) or had contradictions to treatment
• Regorafenib-naïve (have not received regorafenib)
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
• Measurable tumor (≥1 cm longest diameter)
• Acceptable health status as determined by the investigator and blood work (Chemistry, Complete Blood Count, Coagulation)

Exclusion Criteria:

• Intolerant to Irinotecan (if assigned to the combination arm: Cohort 3, Cohort 4 or Combination Expansion Arm)
• Treatment with ketoconazole, enzyme-inducing anticonvulsants and St. John's Wort (if assigned to combination arm)
• Significant immunodeficiency due to underlying illness and/or medication
• History of severe exfoliative skin condition requiring systemic therapy within the past 2 years
• Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions
• Active cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months
• Viable Centrual Nervous System (CNS) malignancy associated with clinical symptoms
• Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks for mitomycin c or nitrosoureas)
• Prior participation in any other research protocol involving an investigational medicinal product within 4 weeks prior to first treatment
• Use of prohibited anti-viral medication, interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX 594 dose
• Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to and 48 hours after all JX-594 treatments.
• Pregnant or nursing an infant
• Diagnosis of chronic inflammatory bowel disease and/or bowel obstruction.