TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma

NCT04217473 | Completed Phase 1 DMC

• 1 other identifier: TILT-T215
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 2

Brief Summary

This is an open-label, phase 1, first-in-human (FIH), dose-escalation, multicenter, multinational trial evaluating the safety of oncolytic adenovirus TILT-123 as monotherapy and in association with T-cell therapy with TILs in metastatic melanoma patients.

Conditions

Metastatic Melanoma

Keywords

oncolytic virus; T-cell therapy; immunotherapy; TILT

Outcome Measures

Primary Outcomes (4)

• Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.

  36 days

• Number of Participants with abnormal laboratory values prior to TIL administration.

  36 days

• Number of Participants with vital sign abnormalities prior to TIL administration.

  36 days

• Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events prior to TIL administration.

  Any clinically significant adverse changes on the ECG will be reported as Adverse Events.

  36 days

Study Arms (1)

TILT-123

EXPERIMENTAL

Patients will receive administrations of TILT-123. Patients will also receive Tumor Infiltrating Lymphocytes (TILs) during the treatment phase. 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

TILT-123

Eligibility Criteria

• Age: 18 Years - 75 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, between 18-75 years of age (both included).
• Pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies.
• At least one prior line of medical treatment is required (for example checkpoint inhibitors, kinase inhibitors, interleukin-2). Multiple prior therapies (e.g. surgery, checkpoint inhibitors, kinase inhibitors, interleukin-2, interferon, chemotherapy, radiation) are allowed.
• A \> 9 mm tumor (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 one additional 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.
• Eligible for adoptive T-cell therapy with tumor infiltrating lymphocytes
• Adequate hepatic, cardiac 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
• 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:

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: replacement corticosteroids if e.g. the patient has adrenal insufficiency after prior immunotherapy; pulmonal and topical treatments; up to 20 mg of prednisone/prednisolone.
• History of another active invasive cancer as judged by the investigator within the past 3 years except basalioma.
• Treated with any anti-cancer therapy for melanoma 30 days prior to enrolment. Anti-cancer therapy for melanoma is defined as anti-cancer agents (immunotherapy, signal-transduction inhibitors \[e.g. BRAF and MEK inhibitors\], cytotoxic chemotherapy), radiotherapy and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans.
• Uncontrolled cardiac or vascular diseases.
• History of heart attack or cerebral stroke within the previous 12 months before screening or is not recovered from an older heart attack or cerebral stroke.
• LDH value \> 3 x ULN.
• History of hepatic dysfunction, hepatitis or HIV.
• History of coagulation disorder.
• Any other disease which prevent participation in the opinion of the investigator.
• Female patients who are pregnant, breastfeeding or intends to become pregnant.
• Untreated brain metastases. Treated brain metastases which have not progressed in 3 months prior to screening are allowed.
• Previously treated with any oncolytic adenovirus that was administered intratumorally.
• Previously treated with adoptive cell therapy.
• Allergy to TILT-123, TIL, or ingredients present in the investigational medicinal products.
• Administered an investigational medicinal product or device in another clinical trial within 30 days prior to screening

Sponsors & Collaborators

• TILT Biotherapeutics Ltd.: lead

Study Sites (2)

National Center for Cancer Immune Therapy Herlev Hospital, Copenhagen University

Copenhagen, Denmark

Location

CHU Nantes

Nantes, France

Location

Related Publications (3)

• 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

• Havunen R, Kalliokoski R, Siurala M, Sorsa S, Santos JM, Cervera-Carrascon V, Anttila M, Hemminki A. Cytokine-Coding Oncolytic Adenovirus TILT-123 Is Safe, Selective, and Effective as a Single Agent and in Combination with Immune Checkpoint Inhibitor Anti-PD-1. Cells. 2021 Jan 27;10(2):246. doi: 10.3390/cells10020246.

  PMID: 33513935 DERIVED

• Cervera-Carrascon V, Quixabeira DCA, Havunen R, Santos JM, Kutvonen E, Clubb JHA, Siurala M, Heinio C, Zafar S, Koivula T, Lumen D, Vaha M, Garcia-Horsman A, Airaksinen AJ, Sorsa S, Anttila M, Hukkanen V, Kanerva A, Hemminki A. Comparison of Clinically Relevant Oncolytic Virus Platforms for Enhancing T Cell Therapy of Solid Tumors. Mol Ther Oncolytics. 2020 Mar 19;17:47-60. doi: 10.1016/j.omto.2020.03.003. eCollection 2020 Jun 26.

  PMID: 32322662 DERIVED

MeSH Terms

Conditions

Melanoma

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

Study Officials

• Inge Marie Svane

  CCIT, Herlev Hospital, Copenhagen University

  PRINCIPAL INVESTIGATOR

• Brigitte Dréno

  CHU Nantes, Nantes University Hospital

  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

Model Details: open-label, single arm, dose escalation

Study Record Dates

• First Submitted: December 19, 2019
• First Posted: January 3, 2020
• Study Start: February 26, 2020
• Primary Completion: December 12, 2023
• Study Completion: July 23, 2024
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); DK (1)