TNFα and IL-2 Coding Oncolytic Adenovirus TILT-123 With Lymphocyte-depleting Chemotherapy and TILs in the Treatment of Melanoma

NCT06961786 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: TILT-T2162024-514092-18-00
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, phase 1 trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with lymphocyte-depleting chemotherapy and TILs in metastatic melanoma patients.

Conditions

Metastatic Melanoma

Keywords

oncolytic virus; TILT; immunotherapy

Outcome Measures

Primary Outcomes (4)

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

  Adverse events

  78 days

• Number of Participants with abnormal laboratory values

  Laboratory values

  78 days

• Number of Participants with vital sign abnormalities

  Vital signs

  78 days

• Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events

  Clinically significant abnormalities detected in the evaluation (including for example rate, rhythm, axis calculations and interpretation of P, Q, R, S, T U waves, segments and basic ECG calculations) will be recorded

  78 days

Study Arms (1)

TILT-123, TILs and chemotherapy

EXPERIMENTAL

TILT-123 in combination with lymphocyte-depleting chemotherapy and TILs

Biological: TILT-123; Biological: TIL; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

TIL BIOLOGICAL

Adoptive T cell therapy with TILs

Also known as: Tumor-infiltrating lymphocytes

TILT-123, TILs and chemotherapy

Cyclophosphamide DRUG

Lymphocyte-depleting chemotherapy

Also known as: Cytoxan, cyclophosphane

TILT-123, TILs and chemotherapy

Fludarabine DRUG

Lymphocyte-depleting chemotherapy

Also known as: Fludara

TILT-123, TILs and chemotherapy

TILT-123 BIOLOGICAL

TNFalpha and IL-2 coding oncolytic adenovirus TILT-123

Also known as: Ad5/3-E2F-d24-hTNFa-IRES-hIL2

TILT-123, TILs and chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be 18 to 75 years of age inclusive, at the time of signing the informed consent.
• Patients with pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies.
• Patients who have had at least 1 prior line of medical treatment (eg, checkpoint inhibitors, kinase inhibitors, IL-2). Multiple prior therapies (eg, surgery, checkpoint inhibitors, kinase inhibitors, IL-2, interferon, chemotherapy, radiation) are allowed.
• Patients must have a demonstrated WHO/ECOG performance score of 0-1 at screening.
• A tumor of \>9 mm in diameter (typically a minimum of 1 cm3 in volume), without signs of necrosis, must be available for biopsy/operation to enable growing of TILs.
• At least 1 additional tumor (\>14 mm in diameter) must be available for injections and biopsies for correlative analyses. The disease burden must be evaluable according to RECIST 1.1.
• Patients must have adequate hepatic, cardiac, and renal function as follows:
• Platelets ≥ 100,000/µl and \< 700,000/µl
• Hemoglobin ≥100 g/L
• AST and ALT ≤2.5×ULN
• GFR \>60 mL/min (CKD-EPI)
• Leukocytes (WBC) \>3.0G/L
• Absolute neutrophil count greater than 1500/mm3 without the support of filgrastim
• Bilirubin \<1.5×ULN
• Patients of 60 years or older, or have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, heart block, will undergo cardiac evaluation: LVEF assessment with documented LVEF ≥ 50% by either TTE (trans thoracal echocardiography) or MUGA (multigated acquisition scan). Further cardiac evaluations in patients with cardiac risk factors (e.g. diabetes, hypertension, obesity) will be evaluated by the investigator as deemed necessary.

You may not qualify if:

• History of another active invasive cancer as judged by the investigator within the past 3 years except basal cell carcinoma.
• Uncontrolled cardiac or vascular diseases.
• History of heart attack or cerebral stroke within the previous 12 months before screening or is not recovered from a previous heart attack or cerebral stroke.
• History of hepatic dysfunction, hepatitis, or human immunodeficiency virus.
• Patients should be seronegative for HIV antibody.
• Patients should be seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
• History of coagulation disorder.
• Untreated brain metastases. Treated brain metastases that have not progressed in the 3 months prior to screening are allowed.
• Concurrent opportunistic and/or active systemic infections.
• Use of immunosuppressive medications (corticosteroids or drugs used in treatment of autoimmune disease), except for the following, which can be allowed at screening and during the study:
• Replacement corticosteroids (eg, if the patient has adrenal insufficiency after prior immunotherapy)
• Pulmonary and topical treatments
• Prednisone/prednisolone at doses up to 20 mg/day
• Treated with any anticancer therapy (eg, immunotherapy, signal-transduction inhibitors \[eg. BRAF and MEK inhibitors\], cytotoxic chemotherapy, radiotherapy, or investigational agents \[ie, any drug or therapy that is currently not approved for use in humans\]) within 30 days prior to enrollment.
• Previously treated with any oncolytic adenovirus that was administered IT.

Sponsors & Collaborators

• TILT Biotherapeutics Ltd.: lead

Study Sites (1)

National Center for Cancer Immune Therapy Herlev Hospital, Copenhagen University

Copenhagen, Denmark

Location

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Inge Marie Svane

  CCIT, Herlev Hospital, Copenhagen University

  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: April 23, 2025
• First Posted: May 8, 2025
• Study Start: June 25, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)