MelanomaPhase 1AVENTILNCT05222932
Oncolytic Adenovirus TILT-123 and Avelumab for Treatment of Solid Tumors Refractory to or Progressing After Anti-PD(L)1
A Phase 1 study testing TILT-123 and Avelumab in people with Melanoma and Head and Neck Squamous Cell Carcinoma, run by TILT Biotherapeutics Ltd. at 2 sites in 2 countries.
Trial summary
This is a phase 1, dose-escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with avelumab in patients with advanced solid tumors refractory to or progressing after anti-PD(L)1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- TILT-123 and Avelumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 8 Mar 2023to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject must be over 18 years of age
- Subject must have pathologically confirmed refractory or recurrent injectable solid tumor (melanoma or SCCHN), which cannot be treated with curative intent with available therapies and is refractory to or progressing after anti-PD(L)1 immunotherapy.
- 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). Multiple prior therapies (eg. surgery, chemotherapy, radiation, checkpoint inhibitors, kinase inhibitors, biological therapies) are allowed.
- At least one tumor lesion of 15 mm or bigger must be available for biopsy and injections that, in the opinion of the investigator, is accessible to repeated injections and biopsies without major safety concerns.
- The disease burden must be evaluable, but does not need to fulfil RECIST 1.1
- Patients must have received at least 6 weeks of prior PD-1/PDL-1 blocking antibody therapy (e.g. 3x 2w cycle or 3x 3w cycle) within the past up to 12 months
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- Patients must have experienced unequivocally documented radiographic progression of disease during or within 6 weeks after the last dose of such treatment.
- Subject must have adequate hepatic and renal functions, including the following laboratory parameters:
- 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 device or hormonal contraception (oral contraceptive pills, implant, transdermal patches, vaginal ring 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.
- Subject must demonstrate a WHO/ECOG performance score of 0-1
- Subject must have life expectancy longer than 3 months according to investigator assessment
- Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent approved by the Independent Ethics committee prior to the initiation of any screening or study -specific procedure.
Who cannot join
- Prior organ transplantation including allogenic stem-cell transplantation or subject is using systemic immunosuppressive medications (eg. 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/d of prednisone/prednisolone (or equivalent).
- 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, biological therapies) and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans. Continuation 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.
- Subject has a history of another active invasive cancer within the past 5 years, except curatively treated basalioma or squamous cell carcinoma of the skin
- Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Subject has a history of interstitial parenchymal lung disease.
- Subject has a LDH value > 3 x ULN (melanoma)
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- Subject has a history of severe hepatic dysfunction, hepatitis, HIV or other severe chronic but active infectious diseases requiring systemic therapy, e.g. tuberculosis
- Subject is using proton pump inhibitors or antibiotics during screening period
- Subject has a history of a coagulation disorder or abnormality in coagulation parameters, as defined by an international normalized ratio not within the normal range, or has received oral or parenteral anticoagulants or thrombolytic agents for therapeutic or prophylactic purposes (including coumadin and warfarin) within 10 days of the first dose of the study treatments. Low molecular weight heparin is permitted if the international normalized ratio is within the normal range
- 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.
- Subject is pregnant, breastfeeding or intend to become pregnant
- Subject has untreated brain metastases. Treated and asymptomatic brain metastases which have not progressed in 3 months prior to study entry are allowed.
- Any known or suspected allergy to TILT-123 or ingredients present in the drug product as listed in this protocol.
- Any known or suspected allergy to avelumab or ingredients present in the drug product as listed in summary of product characteristics (SmPC), including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE Grade ≥ 3).
- Known current alcohol or drug abuse
- Vaccination with live vaccines in the past 30 days prior to start of investigational treatment
- History of immune-related adverse events to previous immunotherapy which led to discontinuation from treatment
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Phase I Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and IL-2 Coding Oncolytic Adenovirus TILT-123 and Avelumab in Solid Tumor Patients (Melanoma and SCCHN) Refractory to or Progressing After Anti-PD(L)1
This is a phase 1, dose-escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with avelumab in patients with advanced solid tumors refractory to or progressing after anti-PD(L)1.
Read the detailed description
This is an open-label, phase 1, dose-escalation trial evaluating the safety of TILT-123 TILT-123 in combination with avelumab in patients with advanced solid tumors (SCCHN and melanoma) refractory to or progressing after anti-PD(L)1. TILT-123 is an oncolytic adenovirus coding for tumor necrosis factor alpha and interleukin 2. The trial is conducted in Helsinki (Finland).
- Conditions
- Melanoma, Head and Neck Squamous Cell Carcinoma
- Being tested
- TILT-123, Avelumab
- Keywords
- oncolytic virus, immunotherapy, immune checkpoint inhibitor
- Medical subject headings
- Melanoma, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TILT-123Biological
Also called TNFalpha and IL-2 coding oncolytic adenovirus TILT-123, Ad5/3-E2F-d24-hTNFa-IRES-hIL2
TNFalpha and IL-2 coding oncolytic adenovirus TILT-123
AvelumabDrug
Also called anti-PD-L1 monoclonal antibody
Anti-PDL1 antibody
| Study group | Role | What they receive |
|---|---|---|
| TILT-123 and avelumab | Experimental | Patients will receive multiple administrations of TILT-123 and avelumab.
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; Drug: Avelumab |
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.
Safety I
Measured: 85 days
Number of Participants with abnormal laboratory values.
Safety II
Measured: 85 days
Number of Participants with vital sign abnormalities.
Safety III
Measured: 85 days
Number of Participants with Adverse Events assessed by 12- lead electrocardiograms (ECGs)
Safety IV
Measured: 85 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2022
- Study start8 Mar 2023
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TILT Biotherapeutics Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tuomo Alanko, Principal investigator, Docrates Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05222932
- Sponsor's protocol ID
- TILT-T776
- Acronym
- AVENTIL
- Status last verified
- Oct 2026
- First submitted
- 1 Feb 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Open-Label, Dose-escalation Clinical Trial of Tumor Necrosis Factor Alpha and IL-2 Coding Oncolytic Adenovirus TILT-123 and Avelumab in Solid Tumor Patients (Melanoma and SCCHN) Refractory to or Progressing After Anti-PD(L)1
- ClinicalTrials.gov ID
- NCT05222932
- Acronym / sponsor ID
- AVENTIL / TILT-T776
- Conditions
- Melanoma, Head and Neck Squamous Cell Carcinoma
- Keywords
- oncolytic virus, immunotherapy, immune checkpoint inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- TILT Biotherapeutics Ltd.Industry (pharma, biotech, devices)
- Study start
- 8 Mar 2023 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 3 Feb 2022 (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 a phase 1, dose-escalation trial evaluating the safety of oncolytic adenovirus TILT-123 in combination with avelumab in patients with advanced solid tumors refractory to or progressing after anti-PD(L)1.
Detailed description
This is an open-label, phase 1, dose-escalation trial evaluating the safety of TILT-123 TILT-123 in combination with avelumab in patients with advanced solid tumors (SCCHN and melanoma) refractory to or progressing after anti-PD(L)1. TILT-123 is an oncolytic adenovirus coding for tumor necrosis factor alpha and interleukin 2. The trial is conducted in Helsinki (Finland).
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 and avelumab | Experimental | Biological: TILT-123, Drug: AvelumabPatients will receive multiple administrations of TILT-123 and avelumab. 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 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Subject must be over 18 years of age
- Subject must have pathologically confirmed refractory or recurrent injectable solid tumor (melanoma or SCCHN), which cannot be treated with curative intent with available therapies and is refractory to or progressing after anti-PD(L)1 immunotherapy.
- 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). Multiple prior therapies (eg. surgery, chemotherapy, radiation, checkpoint inhibitors, kinase inhibitors, biological therapies) are allowed.
- At least one tumor lesion of 15 mm or bigger must be available for biopsy and injections that, in the opinion of the investigator, is accessible to repeated injections and biopsies without major safety concerns.
- The disease burden must be evaluable, but does not need to fulfil RECIST 1.1
Key exclusion criteria (17 listed)
- Prior organ transplantation including allogenic stem-cell transplantation or subject is using systemic immunosuppressive medications (eg. 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/d of prednisone/prednisolone (or equivalent).
- 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, biological therapies) and investigational agents. An investigational agent is any drug or therapy that is currently not approved for use in humans. Continuation 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.
- Subject has a history of another active invasive cancer within the past 5 years, except curatively treated basalioma or squamous cell carcinoma of the skin
- Clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
- Subject has a history of interstitial parenchymal lung disease.
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-123Also: TNFalpha and IL-2 coding oncolytic adenovirus TILT-123, Ad5/3-E2F-d24-hTNFa-IRES-hIL2TNFalpha and IL-2 coding oncolytic adenovirus TILT-123 | Biological | TILT-123 and avelumab |
| AvelumabAlso: anti-PD-L1 monoclonal antibodyAnti-PDL1 antibody | Drug | TILT-123 and avelumab |
Primary outcome
Number of Participants with any (serious and non-serious) Adverse Events.
Time frame: 85 days
Safety I
Number of Participants with abnormal laboratory values.
Time frame: 85 days
Safety II
Number of Participants with vital sign abnormalities.
Time frame: 85 days
Safety III
Number of Participants with Adverse Events assessed by 12- lead electrocardiograms (ECGs)
Time frame: 85 days
Safety IV
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- 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.
Tuomo Alanko principal investigator
Docrates Cancer Center
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 and Avelumab in people with Melanoma and Head and Neck Squamous Cell Carcinoma, 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 21 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 13 Oct 2026. 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 United States, Finland. 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?
This study is still under way. Results are not available in the source record yet.
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. (time frame: 85 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?
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 13 Oct 2026; AzTrials last refreshed its copy on 8 Nov 2026.