TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 Monotherapy

A Phase 1, Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and Interleukin-2 Coding Oncolytic Adenovirus (TILT-123) in Patients With Injectable Solid Tumors

This is an open-label, phase 1, dose-escalation, multicenter trial evaluating the safety of oncolytic adenovirus TILT-123 as monotherapy in advanced solid tumor patients.

This is an open-label, phase 1, dose-escalation trial evaluating the safety of TILT-123 as monotherapy in advanced solid tumor patients. TILT-123 is an oncolytic adenovirus coding for tumor necrosis factor alpha and interleukin 2. The trial includes 2 healthcare centers in Helsinki (Finland). Patients with different indications are expected to be treated in the trial.

Inclusion Criteria:

• Signed and dated informed consent before any trial-related activities.

• Male or female over 18 years of age

• Pathologically confirmed refractory or recurrent injectable solid tumor, which cannot be treated with curative intent with available therapies.

• Standard therapy has failed, it does not exist, is not available or is unlikely to result in meaningful clinical benefit (as assessed by the investigator). Other appropriate evidence-based therapies have failed or are contraindicated.

• Multiple prior therapies (e.g. surgery, chemotherapy, checkpoint inhibitors, kinase inhibitors, biological therapies, hormonal therapies, radiation, etc) are allowed.

• At least one tumor (>14 mm in diameter) must be available for injections and biopsies for correlative analyses. The disease burden must be measurable, but does not need to fulfil RECIST 1.1.

• Adequate hepatic and renal functions as following:

  1. Platelets > 75 000/mm3
  2. Haemoglobin ≥ 100 g/L.
  3. AST and ALT < 3 x ULN.
  4. GFR >60 ml/min (Cockcroft-Gault formula).
  5. Leukocytes (WBC) > 3,0
  6. Bilirubin <1,5 x ULN 8. Men and women must be willing to use adequate forms of contraception from screening, during the trial, and for a minimum of 90 days after end of treatment, in accordance with the following:
  1. Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be used in addition to one of the following methods: Intrauterine device or hormonal contraception (oral contraceptive pills, implant, transdermal patches, vaginal ring or long-acting injections).
  2. Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used.
  3. Men: Barrier contraceptive method (i.e. condom) must be used.

• Demonstrated WHO/ECOG performance score of 0-1 at screening.

• Life expectancy time longer than 3 months.

• Capable of understanding and complying with parameters as outlined in the protocol.

Exclusion Criteria:

• Use of immunosuppressive medications (corticosteroids or drugs used in treatment of autoimmune disease). Exempted are the following which can be allowed at screening and during the trial: a) replacement corticosteroids if e.g. the patient has adrenal insufficiency after prior immunotherapy b) inhaled and topical treatments c) up to 20 mg per day of prednisone/prednisolone.
• Treated with any anti-cancer therapy within 30 days prior to the first virus injection. Anti-cancer therapy is defined as anti-cancer agents (e.g. cytotoxic chemotherapy, immunotherapy, signal-transduction inhibitors, etc) and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans. Continuation of hormonal therapy or use of bone modifying agents (eg. bisphosphonate or denosumab) is allowed if started at least 3 months before. Palliative radiation is not allowed within 14 days of the first virus injection (before or after), but it is allowed after day 15 during the trial treatment period, if deemed necessary by the investigator.
• Uncontrolled cardiac or vascular diseases.
• History of myocardial infarction or cerebral stroke within the previous 12 months before screening or is not sufficiently recovered from an older infarction or cerebral stroke.
• History of severe hepatic dysfunction, hepatitis or HIV.
• History of coagulation disorder.
• Any other medical condition or laboratory abnormality that in the judgment of the principal investigator, may increase the risk associated with study participation or may interfere with interpretation of study results and /or otherwise make the patient inappropriate for entry into this trial.
• Female patients who are pregnant, breastfeeding or intend to become pregnant.
• Untreated brain metastases. Treated brain metastases which have not progressed in 3 months prior to screening are allowed.
• Previously treated (within 5 years) with any oncolytic or replication deficient adenovirus.
• Allergy to ingredients present in the investigational medicinal products (ingredients are listed in the protocol).