TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 Monotherapy (TUNIMO)

• ClinicalTrials.gov Identifier: NCT04695327
• Recruitment Status: Recruiting
• First Posted: January 5, 2021
• Last Update Posted: April 12, 2023
• Sponsor: TILT Biotherapeutics Ltd.
• Information provided by (Responsible Party): TILT Biotherapeutics Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Biological: TILT-123	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 11, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: March 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Monotherapy; Patients will receive multiple administrations of TILT-123. Escalation to the next dose of TILT-123 level will occur when the safety data has been evaluated for all patients in the preceding dose level.	Biological: TILT-123; TNFalpha and IL-2 coding oncolytic adenovirus TILT-123; Other Names: TNFalpha and IL-2 coding oncolytic adenovirus TILT-123; Ad5/3-E2F-d24-hTNFa-IRES-hIL2

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with any (serious and non-serious) Adverse Events. [ Time Frame: 85 days ]
   Safety (I)
2. Number of Participants with abnormal laboratory values. [ Time Frame: 85 days ]
   Safety (II)
3. Number of Participants with vital sign abnormalities. [ Time Frame: 85 days ]
   Safety (III)
4. Number of Participants with Adverse Events assessed by 12- lead electrocardiograms (ECGs) [ Time Frame: 85 days ]
   Safety (IV)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Contacts

Contact: Docrates Cancer Center; +358 107732050; hospital@docrates.com

Contact: Helsinki University Hospital; +358 947173197

Locations

Finland

Helsinki University Hospital; Recruiting

Helsinki, Uusima, Finland, 00029

Contact: Katriina Peltola, MD, PhD

Docrates Cancer Center; Recruiting

Helsinki, Uusima, Finland, 00180

Contact: Tuomo Alanki, MD, PhD

Sponsors and Collaborators

TILT Biotherapeutics Ltd.

Investigators

• Principal Investigator: Katriina Peltola, MD, PhD; Helsinki University Central Hospital
• Principal Investigator: Tuomo Alanko, MD, PhD; Docrates Cancer Center

More Information

• Responsible Party: TILT Biotherapeutics Ltd.
• ClinicalTrials.gov Identifier: NCT04695327
• Other Study ID Numbers: TILT-T115; 2020-001778-31 ( EudraCT Number )
• First Posted: January 5, 2021
• Last Update Posted: April 12, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by TILT Biotherapeutics Ltd.:

Oncolytic virus; Virotherapy; Immunotherapy; Adenovirus; TILT-123

Additional relevant MeSH terms:

Adenoviridae Infections; DNA Virus Infections; Virus Diseases; Infections