Study of Intrahepatic Arterial Infusion of TG6002 in Combination With 5-FC in Patients With Metastatic Colorectal Cancer

A Dose-escalation and Phase IIa Study of TG6002 Plus Flucytosine in Patients With Unresectable Colorectal Cancer With Liver Metastases

This study will include two parts:

• Phase I part is a dose-escalation study to assess the safety of increasing doses of TG6002 in combination with oral flucytosine (5-FC) in consecutive cohorts of 3 to 6 patients with colorectal cancer and unresectable liver metastases according to a 3+3 design
• Phase IIa part is an extension of the phase I part at the recommended phase II dose to evaluate the efficacy of TG6002 in combination with oral flucytosine (5-FC) in patients with colorectal cancer and unresectable liver metastases.

In both parts, tumor response will be evaluated on local assessment using RECIST 1.1.

All patients will be followed until disease progression, death due to any cause or the date of data cut-off, whichever occurs first.

Inclusion Criteria:

1. Unresectable metastatic CRC with at least one measurable liver metastasis
2. At least one liver metastasis amenable to biopsy
3. Patients previously exposed to fluoropyrimidine-based chemotherapy
4. (Phase I) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy, or, in the UK only, patients on or entering a period of clinical observation without treatment
5. (Phase IIa) Patients having failed, are intolerant to, or unsuitable for both oxaliplatin and irinotecan-based chemotherapy.
6. Aged ≥18 years
7. Estimated life expectancy >3 months
8. ECOG performance status ≤1

Exclusion Criteria:

1. Predominant extrahepatic disease
2. Symptomatic brain metastases or meningeal tumors
3. Any contraindication to intrahepatic artery infusion procedure
4. Received other investigational therapy or had surgery within 4 weeks of treatment initiation which would interfere with study treatment
5. Received locoregional therapy for CRC within 4 weeks prior to treatment initiation
6. Severe uncontrolled coagulopathy OR anticoagulant medication
7. Antiviral therapy active on vaccinia virus, e.g., ribavirin, interferon/pegylated interferon
8. Immunosuppression due to immunosuppressive medication including steroids equivalent to prednisolone >10mg/day taken for more than 4 weeks within 3 months prior to TG6002 treatment initiation
9. Patients treated with 3 or more anti-hypertensive agents AND/OR patients with signs of advanced hypertensive disease, such as left ventricular hypertrophy, hypertensive encephalitis or history of hemorrhagic stroke.