Phase I / II Study of Enadenotucirev by Sub-acute Fractionated IV Dosing in Cancer Patients

Inclusion criteria

• Patients must provide written informed consent
• Age ≥ 18 years and the patient must be at least the legal age limit to be able to give consent within the jurisdiction the study is taking place.
• ECOG performance status 0 or 1
• Predicted life expectancy of 3 months or more
• Ability to comply with study procedures in the Investigator's opinion
• Recovered to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
• Adequate renal function

• Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance using the Cockcroft-Gault formula ≥ 60 mL/min, or measured creatinine clearance ≥ 60 mL/min, Haematuria: dipstick ≤ 2+
• Proteinuria: dipstick ≤ 2+
• Adequate hepatic function

• Serum bilirubin < 1.5 mg/dL
• Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3x upper limit of normal (ULN)
• Adequate bone marrow function:

• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 100 g/L for UCC and ≥ 90 g/L for other cancers
• Adequate coagulation tests: international normalised ratio (INR) ≤ 1.5 x ULN
• For females of childbearing potential (defined as <2 years after last menstruation or not surgically sterile), a negative serum pregnancy test must be documented within 14 days prior to first administration of study treatment
• For women who are not postmenopausal (24 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two adequate methods of contraception, during the treatment period and for at least 3 months after the last dose of study drug
• For men: agreement to use a barrier method of contraception during the treatment period and for at least 6 months after the last dose of study drug
• At least 3 weeks since any dose of IV systemic chemotherapy and at least two weeks since any oral dose of capecitabine at the time of first administration of ColoAd1.

Phase I Specific Inclusion Criteria:

Dose Escalation Stage only (except Repeat Cycle Cohort):

• Solid tumour of epithelial origin not responding to standard therapy or for whom no standard treatment exists

Dose Expansion Stage Single Cycle and Dose Escalation Stage Repeat Cycle Cohort:

• mCRC not responding to standard therapy
• ≤ 3 prior lines of systemic therapy for advanced disease OR ≤ 4 prior lines of systemic therapy for advanced disease if one of the 4 lines was an anti EGFR therapy given as a single agent or combined to a previously administered chemotherapy regimen Phase Ib:mCRC not responding to standard therapy
• no more than 3 prior lines of systemic therapy for advanced disease OR no more than 4 prior lines of systemic therapy for advanced disease if one of the 4 lines was an anti EGFR therapy given as a single agent or combined to a previously administered chemotherapy regimen
• Advanced or metastatic UCC, who have received a maximum of one chemotherapy-containing regimen and a maximum of one other systemic treatment with biologic agents only.

Phase II Specific Inclusion Criteria:

• mCRC
• Have received 3 - 4 months of first line chemotherapy with either FOLFOX, FOLFIRI or CAPOX, with or without bevacizumab
• At least one measurable lesion according to RECIST 1.1 criteria
• Documented partial response or stable disease
• Eligible to receive chemotherapy with FOLFOX or CAPOX after a short chemotherapy interruption (3 to 4 weeks)

Exclusion criteria

for all Patients:

• Pregnant or breast feeding females;
• Known history or evidence of significant immunodeficiency due to underlying illness (e.g. human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [AIDS]) and/or medication (e.g. systemic corticosteroids, or other immunosuppressive medications including cyclosporine, azathioprine, interferons, within the past 4 weeks)
• Splenectomy
• Prior allogeneic or autologous bone marrow or organ transplantation
• Active infections requiring antibiotics, physician monitoring, or recurrent fevers >38.0 degrees centigrade associated with a clinical diagnosis of active infection
• Active viral disease or known positive serology for HIV, hepatitis B or hepatitis C;
• Use of the following anti-viral agents: ribavirin, adefovir, lamivudine or cidofovir within 7 days prior to day 1; or pegylated interferon (PEG-IFN) (within 14 days prior to first administration of ColoAd1)
• Administration of an investigational drug within 28 days prior to first dose of ColoAd1
• Major surgery within 4 weeks or radiotherapy within 3 weeks prior to first dose of ColoAd1
• Another primary malignancy within the past 3 years (except for non melanoma skin cancer or cervical cancer in situ)
• Central nervous system (CNS) metastasis that is symptomatic and/or requires treatment
• Any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the drug
• Known allergy to treatment medication or its excipients
• Any other medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent

Phase II Specific Exclusion Criteria:

• Progression on first line therapy
• A complete response on first line therapy
• Use of first line therapy for longer than 4 months
• Use of any first line treatment with a chemotherapy regimen other than FOLFOX, FOLFIRI or CAPOX (each with or without bevacizumab)
• More than 6 weeks since the last administration of 5 FU, capecitabine, oxaliplatin or irinotecan