Metastatic MelanomaPhase 1TUNINTILNCT04217473
TNFalpha and Interleukin 2 Coding Oncolytic Adenovirus TILT-123 During TIL Treatment of Advanced Melanoma
A Phase 1 study testing TILT-123 in people with Metastatic Melanoma, run by TILT Biotherapeutics Ltd. at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- TILT-123
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 Feb 2020to 23 Jul 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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:
- Women of childbearing potential: Barrier contraceptive method (i.e. condom) must be used in addition to one of the following methods: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections).
- Women not of childbearing potential: Barrier contraceptive method (i.e. condom) must be used.
- Men: Barrier contraceptive method (i.e. condom) must be used.
- Demonstrated WHO 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.
- BRAF negative or positive.
Who cannot join
- 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.
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- 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
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Denmark1 site
National Center for Cancer Immune Therapy Herlev Hospital, Copenhagen University
Copenhagen
About this study
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 Melanoma Patients Receiving Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes
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.
Read the detailed description
The primary objective of the trial is to evaluate the safety of TILT-123. The approach has the potential to a) increase the efficacy of adoptive T-cell therapy, b) remove the need for toxic pre- and post-conditioning regimens, c) yield the combined anti-tumor benefits of armed oncolytic viruses and T-cell therapy.
Dose escalation of TILT-123 injection will take place between cohorts not intra-patient and will be determined based on Dose Limiting Toxicities (DLTs).
- Conditions
- Metastatic Melanoma
- Being tested
- TILT-123
- Keywords
- oncolytic virus, T-cell therapy, immunotherapy, TILT
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TILT-123Biological
TNFalpha and IL-2 coding oncolytic adenovirus TILT-123
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: TILT-123 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.
Measured: 36 days
Number of Participants with abnormal laboratory values prior to TIL administration.
Measured: 36 days
Number of Participants with vital sign abnormalities prior to TIL administration.
Measured: 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.
Measured: 36 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2020
- Study start26 Feb 2020
- Primary completion12 Dec 2023
- Study completion23 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- open-label, single arm, dose escalation
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- TILT Biotherapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Inge Marie Svane, Principal investigator, CCIT, Herlev Hospital, Copenhagen UniversityBrigitte Dréno, Principal investigator, CHU Nantes, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04217473
- Sponsor's protocol ID
- TILT-T215
- Acronym
- TUNINTIL
- Status last verified
- Aug 2025
- First submitted
- 19 Dec 2019
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Haybout L, Kudling TV, Clubb JH, Monberg TJ, Albieri B, Pakola SA, Jirovec E, Arias V, Quixabeira DCA, Juteau S, Ellebaek E, Donia M, Lovendahl Eefsen R, Borch TH, Lorentzen T, Hendel H, Vestergaard CD, Khammari A, Kistler C, Westergaard MCW, Met O, Sorsa S, Hemminki O, Kanerva A, Cervera-Carrascon V, Dreno B, Svane IM, Hemminki A. Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy. J Immunother Cancer. 2026 Aug 20;14(8):e016003. doi: 10.1136/jitc-2026-016003.
PubMed 42624531Clubb 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 May 6;34(5):3056-3076. doi: 10.1016/j.ymthe.2026.01.019. Epub 2026 Jan 20.
PubMed 41566775Jirovec 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.
PubMed 39506856Havunen 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.
PubMed 33513935Cervera-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.
PubMed 32322662
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Melanoma Patients Receiving Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes
- ClinicalTrials.gov ID
- NCT04217473
- Acronym / sponsor ID
- TUNINTIL / TILT-T215
- Conditions
- Metastatic Melanoma
- Keywords
- oncolytic virus, T-cell therapy, immunotherapy, TILT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- TILT Biotherapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 12 Dec 2023 (actual)
- Study completion
- 23 Jul 2024 (actual)
- First posted
- 3 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The primary objective of the trial is to evaluate the safety of TILT-123. The approach has the potential to a) increase the efficacy of adoptive T-cell therapy, b) remove the need for toxic pre- and post-conditioning regimens, c) yield the combined anti-tumor benefits of armed oncolytic viruses and T-cell therapy.
Dose escalation of TILT-123 injection will take place between cohorts not intra-patient and will be determined based on Dose Limiting Toxicities (DLTs).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open-label, single arm, dose escalation
| Arm | Type | Receives |
|---|---|---|
| TILT-123 | Experimental | Biological: TILT-123Patients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TILT-123TNFalpha and IL-2 coding oncolytic adenovirus TILT-123 | Biological | TILT-123 |
Primary outcome
Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration.
Time frame: 36 days
Number of Participants with abnormal laboratory values prior to TIL administration.
Time frame: 36 days
Number of Participants with vital sign abnormalities prior to TIL administration.
Time frame: 36 days
Safety assessed by 12- lead electrocardiograms (ECGs) Adverse Events prior to TIL administration.
Time frame: 36 days
Any clinically significant adverse changes on the ECG will be reported as Adverse Events.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Derived from this study: PubMed 42624531Haybout L, Kudling TV, Clubb JH, Monberg TJ, Albieri B, Pakola SA, Jirovec E, Arias V, Quixabeira DCA, Juteau S, Ellebaek E, Donia M, Lovendahl Eefsen R, Borch TH, Lorentzen T, Hendel H, Vestergaard CD, Khammari A, Kistler C, Westergaard MCW, Met O, Sorsa S, Hemminki O, Kanerva A, Cervera-Carrascon V, Dreno B, Svane IM, Hemminki A. Immune-cytokine signature predicts survival in patients with advanced melanoma treated with oncolytic adenovirus TILT-123 and chemotherapy and IL-2-free adoptive TIL therapy. J Immunother Cancer. 2026 Aug 20;14(8):e016003. doi: 10.1136/jitc-2026-016003.
- Derived from this study: PubMed 41566775Clubb 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 May 6;34(5):3056-3076. doi: 10.1016/j.ymthe.2026.01.019. Epub 2026 Jan 20.
- Derived from this study: PubMed 39506856Jirovec 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.
- Derived from this study: PubMed 33513935Havunen 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.
- Derived from this study: PubMed 32322662Cervera-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Inge Marie Svane principal investigator
CCIT, Herlev Hospital, Copenhagen University
Brigitte Dréno principal investigator
CHU Nantes, Nantes University Hospital
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TILT-123 in people with Metastatic Melanoma, run by TILT Biotherapeutics Ltd. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with any (serious and non-serious) Adverse Events prior to TIL administration. (time frame: 36 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04217473, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.