ONCOS-102 (Previously CGTG-102) for Therapy of Advanced Cancers

Exploratory Open Label Study of GM-CSF Coding Oncolytic Adenovirus CGTG-102, With Low Dose Cyclophosphamide in Patients With Refractory Injectable Solid Tumours

The purpose of the study is to investigate the safety and the recommended dose for later use of an oncolytic adenovirus CGTG-102 in combination with low-dose oral cyclophosphamide in the treatment of advanced cancers.

CGTG-102 is an adenovirus that has been armed with granulocyte-macrophage colony stimulating factor (GMCSF), a potent stimulator of immunological cells.

With regard to oncolytic viruses, replication in normal cells does not take place, and therefore viruses such as CGTG-102 are not known to cause any disease. Further, to date there has been no incidence of passing the virus on to other humans from patients. Since the virus requires tumor cells to multiply, such events are unlikely.

To this day more than 100 patients have been treated with CGTG-102. This clinical trial will take place over approximately 6 months. The study includes 12 visits to the hospital, 1 screening visit, 9 injection visits including overnight stay at the hospital(performed on trial days 1, 4, 8, 15, 29, 57, 85, 113 and 141), 1 end of treatment visit (day 169) and 1 end of study visit (day 190). Oral treatment with cyclophosphamide (1 pill per day) will start on the day after the first injection and last until visit day 169.

Inclusion Criteria:

1. Solid tumour refractory to evidence-based oncological therapies.

2. Age 18 years and over.

3. At least one tumour mass measurable by PET (i.e. PET-positive lesion that can reliably be assessed for SUVmax, typically featuring longest diameter ≥2 cm).

4. Tumour is injectable i.t. by direct visualisation/palpation or by imaging-guidance (ultrasound). I.t. includes intracavitary injections, particularly intraperitoneal and intrapleural.

5. Histological confirmation of primary disease or relapse.

6. Patient has given signed informed consent.

7. WHO performance score 0-1 and life expectancy more than 3 months.

8. Previous anti-cancer treatment at least 1 month before Day 1.

9. Tumour assessed to be suitable for biopsy.

10. Hepatic, renal and bone marrow functions within normal limits for the target population as indicated by the following:

    • Total bilirubin ≤ the upper limit of normal (ULN).

    • ASAT, ALAT ≤3.0 × ULN.

    • Serum creatinine ≤1.5 x ULN.

    • International normalised ratio (INR) ≤1.5 x ULN.

    • Haematologic parameters: Patients can be transfused to meet the haemoglobin and platelet count entry criteria.

      • Haemoglobin ≥10 g/dL
      • Leucocytes ≥2.3 x 109/L
      • Platelet count ≥7.5 x 109/L

Exclusion Criteria:

1. Use of high dose systemic immune suppressive medication within 3 weeks of anticipated first treatment. Note: patients taking low-dose corticosteroids for the treatment of nausea and/or taking maintenance corticosteroids are permitted to enrol.
2. Known infection with HIV or known underlying genetic immunodeficiency disease as these might affect the safety and efficacy of treatment.
3. Treatment of the injected tumour(s) with radiotherapy, chemotherapy, surgery, or an investigational drug within 4 weeks prior to the first treatment.
4. Recent thromboembolic event (deep venous thrombosis, pulmonary embolism).
5. Clinically significant active infection or clinically significant medical condition considered high risk for investigational new drug treatment (e.g. pulmonary, neurological, cardiovascular, metabolic, clinically significant and/or rapidly accumulating pericardial effusion).
6. Severe or unstable cardiac disease.
7. Known brain metastases, glioma. Central nervous system malignancy, including carcinomatosis meningitis.
8. Pulse oximetry oxygen saturation <90% at rest in room air.
9. Vaccination with a live virus (i.e. measles, mumps, rubella, etc.) <30 days prior to the first treatment.
10. History of hepatic dysfunction, cirrhosis or hepatitis.
11. Prior organ transplant.
12. Pregnant or lactating patients.
13. Evidence of coagulation disorder.
14. Other conditions which, in the opinion of the investigator, might interfere with the study findings or represent a safety hazard for the patient.