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

NCT04695327 | Completed Phase 1 DMC

• 2 other identifiers: TILT-T1152020-001778-31
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

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.

Conditions

Solid Tumor

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Number of Participants with any (serious and non-serious) Adverse Events.

  Safety (I)

  85 days

• Number of Participants with abnormal laboratory values.

  Safety (II)

  85 days

• Number of Participants with vital sign abnormalities.

  Safety (III)

  85 days

• Number of Participants with Adverse Events assessed by 12- lead electrocardiograms (ECGs)

  Safety (IV)

  85 days

Study Arms (1)

Monotherapy

EXPERIMENTAL

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

Interventions

TILT-123 BIOLOGICAL

TNFalpha and IL-2 coding oncolytic adenovirus TILT-123

Also known as: TNFalpha and IL-2 coding oncolytic adenovirus TILT-123, Ad5/3-E2F-d24-hTNFa-IRES-hIL2

Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Platelets \> 75 000/mm3
• Haemoglobin ≥ 100 g/L.
• AST and ALT \< 3 x ULN.
• GFR \>60 ml/min (Cockcroft-Gault formula).
• Leukocytes (WBC) \> 3,0
• 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:
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• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• TILT Biotherapeutics Ltd.: lead

Study Sites (2)

Helsinki University Hospital

Helsinki, Uusima, 00029, Finland

Location

Docrates Cancer Center

Helsinki, Uusima, 00180, Finland

Location

Related Publications (2)

• Clubb JHA, Pakola SA, Joenvaara S, Kudling TV, Tohmola T, Arias V, Jirovec E, van der Heijden M, Quixabeira DCA, Pasanen A, Haybout L, Ojala N, Basnet S, Eleuteri A, Ferrero JD, Hirvenoja S, Svane IM, Maenpaa J, Jalkanen K, Block MS, Alanko T, Monberg T, Zahraoui S, Gronberg-Vaha-Koskela S, Salmelin N, Kistler C, Havunen R, Sorsa S, Manuel Dos Santos J, Cervera-Carrascon V, Kanerva A, Hemminki O, Renkonen R, Hemminki A. Dyslipidemia-associated natural IgM improves oncolytic virus TILT-123 efficacy through antibody-dependent enhancement in solid tumors. Mol Ther. 2026 Jan 20:S1525-0016(26)00020-1. doi: 10.1016/j.ymthe.2026.01.019. Online ahead of print.

  PMID: 41566775 DERIVED

• Jirovec E, Quixabeira DCA, Clubb JHA, Pakola SA, Kudling T, Arias V, Haybout L, Jalkanen K, Alanko T, Monberg T, Khammari A, Dreno B, Svane IM, Block MS, Adamo DA, Maenpaa J, Kistler C, Sorsa S, Hemminki O, Kanerva A, Santos JM, Cervera-Carrascon V, Hemminki A. Single intravenous administration of oncolytic adenovirus TILT-123 results in systemic tumor transduction and immune response in patients with advanced solid tumors. J Exp Clin Cancer Res. 2024 Nov 6;43(1):297. doi: 10.1186/s13046-024-03219-0.

  PMID: 39506856 DERIVED

MeSH Terms

Conditions

Adenoviridae Infections

Interventions

Tumor Necrosis Factor-alpha

Condition Hierarchy (Ancestors)

DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Monokines; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Tumor Necrosis Factors; Blood Proteins; Proteins; Biological Factors

Study Officials

• Katriina Peltola, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

• Tuomo Alanko, MD, PhD

  Docrates Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 5, 2021
• Study Start: January 11, 2021
• Primary Completion: September 3, 2025
• Study Completion: September 3, 2025
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FI (2)