Uveal MelanomaPhase 1/2SILVERNCT07063875
Adding IL-2 to Tebentafusp to Eradicate Cancer Progression
A Phase 1/2 study testing Aldesleukin in people with Uveal Melanoma and Metastatic Uveal Melanoma, run by St Vincent's Hospital, Sydney at 2 sites in Australia.
Trial summary
A recent clinical trial found that after 36 months, patients taking tebentafusp had a median survival of 21.6 months, compared to 16.9 months for those in the control group. Since recruitment for tebentafusp in metastatic uveal melanoma (mUM) has ended, a new trial is starting to test whether adding IL-2 can help… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma, Metastatic Uveal Melanoma, Metastatic Uveal Melanoma in the Liver
- What is being tested?
- Aldesleukin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 2 sitesAustralia
- Study dates
- 1 Jun 2025to Sep 2027
- Phase
- Phase 1/2
- 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
- Histologically or cytologically confirmed metastatic UM or unresectable UM patients
- HLA-A*02:01 positive
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- RECIST 1.1 defined progression on single-agent Tebentafusp, with no other intervening systemic therapies
Who cannot join
- Presence of untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or cord compression. (NOTE: Participants with treated CNS lesions may enroll provided all of the following apply: Treated CNS lesions must be radiographically stable for ≥ 4 weeks after intervention (surgery and/or radiation). Participants must be neurologically stable off systemic corticosteroids for at least 2 weeks prior to trial entry, AND Greater than 14 days elapsed between the last dose of previous Tebentafusp and first dose of IL-2 on trial)
- Systemic treatment with steroids or any other immunosuppressive drug use within 2 weeks of the planned first dose of program intervention, with the following exceptions: Treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 10 mg daily or the equivalent; Local steroid therapies (eg, optic, ophthalmic, intra- articular, or inhaled medications) are acceptable.
- Any relevant medical condition, which in the opinion of the treating physician, would prevent the participant enrolling into the Program due to concerns related to safety, compliance with procedures, or interpretation of program results.
- Chronic viral infections as indicated below. NOTE: Testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) status prior to enrollment is not necessary unless clinically indicated.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Australia2 sites, 2 recruiting
- Not yet recruiting
Alfred Hospital
Melbourne, Victoria, 3004
Mark Shackleton, MBBS PhD
- Recruiting
Kinghorn Cancer Centre, St. Vincent's Hospital
Sydney, New South Wales, 2010
Robert Kent, 0293555611, SVHS.CancerResearch@svha.org.au
About this study
Official title: Supplementing With IL-2 to Verifiably eRadicate Radiological Progression
A recent clinical trial found that after 36 months, patients taking tebentafusp had a median survival of 21.6 months, compared to 16.9 months for those in the control group. Since recruitment for tebentafusp in metastatic uveal melanoma (mUM) has ended, a new trial is starting to test whether adding IL-2 can help overcome resistance to tebentafusp and improve its effectiveness.
This study aims to answer:
Read more
- Can combining tebentafusp with IL-2 improve tumor response and overall survival?
- What are the benefits and side effects of this combination therapy?
All participants will receive both IL-2 and tebentafusp in a 28-day treatment cycle. The dosing schedule is as follows:
Cycle1:
Day1-3 IL-2 Day4 Tebentafusp Day 10 IL-2 Day 11 Tebentafusp Day 17 IL-2 Day 18 Tebentafusp Day 24 IL-2 Day 25 Tebentafusp
Cycle 2 \& thereafter Day 1 IL-2 Day 2 Tebentafusp Day 8 IL-2 Day 9 Tebentafusp Day 15 IL-2 Day 16 Tebentafusp Day 22 IL-2 Day 23 Tebentafusp
Read the detailed description
Uveal melanoma (UM) is a rare and highly malignant neoplasm affecting the vascular layers of the eye (iris, ciliary body, or choroid). UM primarily metastasizes to the liver and less commonly to the lungs and bones. Once patients develop mUM, the prognosis is very poor with a median survival of < 12 months. There are limited treatments for mUM that extend survival, and there is no proven standard of care. Enrolment in investigational clinical trials is the treatment option recommended by national and regional guidelines. A clear unmet medical need exists for patients with this serious and life- threatening disease.
Tebentafusp is a bispecific protein therapeutic comprising a soluble, affinity-enhanced T cell receptor (TCR; targeting domain) fused to an antibody single-chain variable fragment (scFv) targeting cluster of differentiation (CD)3 (effector domain). Tebentafusp recognizes a peptide derived from gp100, a melanocyte lineage antigen expressed strongly in tumors derived from melanocytes that is presented on the cell surface by HLA-A*02:01. Once the soluble TCR of tebentafusp is engaged, the scFv effector domain can bind to CD3 on any T cell, redirecting the T cell to produce effector cytokines and kill the cell presenting the target peptide. In addition, tebentafusp-mediated lysis may prime an endogenous antitumor immune response via epitope spreading. This mechanism is distinct from all other therapies that have been studied for melanoma.
The most recent evidence for the utility of Tebentafusp was just published demonstrating that at a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87).
Now that all registrational metastatic trials in UM with Tebentafusp are closed to recruitment, this trial is being initiated to explore the addition of IL2 to offer a mechanism to overcome tebentafusp resistance and explore its efficacy and toxicities.
This Phase Ib study aims to administer tebentafusp in combination with IL-2 to improve primary endpoint of radiographic response rate as well the secondary endpoint of Overall Survival (OS).
- Being tested
- Aldesleukin
- Keywords
- metastatic uveal melanoma, Immunotherapy, Treatment resistance, Combinational immunotherapy
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AldesleukinDrug
Also called Proleukin
IL-2 in combination with Tebentafusp
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Single arm study -all enrolled participants will receive investigational products- IL-2 (Proleukin) and Tebetafusp Receives: Drug: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Combination therapy
As assessed by CTCAE V5.0
Measured: Through study completion, approx 1 year
Secondary outcomes (2)
Radiological progression free survival
Time to RECIST 1.1 progression
Measured: Through study completion, approx 1 year
Overall Survival
Time to Death
Measured: Through study completion, approx 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2025
- Study start1 Jun 2025
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St Vincent's Hospital, Sydney
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anthony Joshua, FRACP, St Vincent's Hospital, Sydney
- Investigators
- Anthony Joshua, FRACP, Principal investigator, St Vincent's Hospital, Sydney
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07063875
- Sponsor's protocol ID
- SILVER Trial
- Acronym
- SILVER
- Status last verified
- Jul 2025
- First submitted
- 17 Jun 2025
- Last updated
- 14 Jul 2025
- 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 14 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Supplementing With IL-2 to Verifiably eRadicate Radiological Progression
- ClinicalTrials.gov ID
- NCT07063875
- Acronym / sponsor ID
- SILVER / SILVER Trial
- Keywords
- metastatic uveal melanoma, Immunotherapy, Treatment resistance, Combinational immunotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- St Vincent's Hospital, SydneyUniversity, hospital or other
- Study start
- 1 Jun 2025 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 14 Jul 2025 (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.
A recent clinical trial found that after 36 months, patients taking tebentafusp had a median survival of 21.6 months, compared to 16.9 months for those in the control group. Since recruitment for tebentafusp in metastatic uveal melanoma (mUM) has ended, a new trial is starting to test whether adding IL-2 can help overcome resistance to tebentafusp and improve its effectiveness.
This study aims to answer:
- Can combining tebentafusp with IL-2 improve tumor response and overall survival?
- What are the benefits and side effects of this combination therapy?
All participants will receive both IL-2 and tebentafusp in a 28-day treatment cycle. The dosing schedule is as follows:
Cycle1:
Day1-3 IL-2 Day4 Tebentafusp Day 10 IL-2 Day 11 Tebentafusp Day 17 IL-2 Day 18 Tebentafusp Day 24 IL-2 Day 25 Tebentafusp
Cycle 2 \& thereafter Day 1 IL-2 Day 2 Tebentafusp Day 8 IL-2 Day 9 Tebentafusp Day 15 IL-2 Day 16 Tebentafusp Day 22 IL-2 Day 23 Tebentafusp
Detailed description
Uveal melanoma (UM) is a rare and highly malignant neoplasm affecting the vascular layers of the eye (iris, ciliary body, or choroid). UM primarily metastasizes to the liver and less commonly to the lungs and bones. Once patients develop mUM, the prognosis is very poor with a median survival of < 12 months. There are limited treatments for mUM that extend survival, and there is no proven standard of care. Enrolment in investigational clinical trials is the treatment option recommended by national and regional guidelines. A clear unmet medical need exists for patients with this serious and life- threatening disease.
Tebentafusp is a bispecific protein therapeutic comprising a soluble, affinity-enhanced T cell receptor (TCR; targeting domain) fused to an antibody single-chain variable fragment (scFv) targeting cluster of differentiation (CD)3 (effector domain). Tebentafusp recognizes a peptide derived from gp100, a melanocyte lineage antigen expressed strongly in tumors derived from melanocytes that is presented on the cell surface by HLA-A*02:01. Once the soluble TCR of tebentafusp is engaged, the scFv effector domain can bind to CD3 on any T cell, redirecting the T cell to produce effector cytokines and kill the cell presenting the target peptide. In addition, tebentafusp-mediated lysis may prime an endogenous antitumor immune response via epitope spreading. This mechanism is distinct from all other therapies that have been studied for melanoma.
The most recent evidence for the utility of Tebentafusp was just published demonstrating that at a minimum follow-up of 36 months, median overall survival was 21.6 months in the tebentafusp group and 16.9 months in the control group (hazard ratio for death, 0.68; 95% confidence interval, 0.54 to 0.87).
Now that all registrational metastatic trials in UM with Tebentafusp are closed to recruitment, this trial is being initiated to explore the addition of IL2 to offer a mechanism to overcome tebentafusp resistance and explore its efficacy and toxicities.
This Phase Ib study aims to administer tebentafusp in combination with IL-2 to improve primary endpoint of radiographic response rate as well the secondary endpoint of Overall Survival (OS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: AldesleukinSingle arm study -all enrolled participants will receive investigational products- IL-2 (Proleukin) and Tebetafusp |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Histologically or cytologically confirmed metastatic UM or unresectable UM patients
- HLA-A*02:01 positive
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- RECIST 1.1 defined progression on single-agent Tebentafusp, with no other intervening systemic therapies
Key exclusion criteria (4 listed)
- Presence of untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or cord compression. (NOTE: Participants with treated CNS lesions may enroll provided all of the following apply: Treated CNS lesions must be radiographically stable for ≥ 4 weeks after intervention (surgery and/or radiation). Participants must be neurologically stable off systemic corticosteroids for at least 2 weeks prior to trial entry, AND Greater than 14 days elapsed between the last dose of previous Tebentafusp and first dose of IL-2 on trial)
- Systemic treatment with steroids or any other immunosuppressive drug use within 2 weeks of the planned first dose of program intervention, with the following exceptions: Treatment for well-controlled and asymptomatic adrenal insufficiency is permitted, but replacement dosing is limited to prednisone ≤ 10 mg daily or the equivalent; Local steroid therapies (eg, optic, ophthalmic, intra- articular, or inhaled medications) are acceptable.
- Any relevant medical condition, which in the opinion of the treating physician, would prevent the participant enrolling into the Program due to concerns related to safety, compliance with procedures, or interpretation of program results.
- Chronic viral infections as indicated below. NOTE: Testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) status prior to enrollment is not necessary unless clinically indicated.
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 |
|---|---|---|
| AldesleukinAlso: ProleukinIL-2 in combination with Tebentafusp | Drug | Treatment arm |
Primary outcome
Safety of Combination therapy
Time frame: Through study completion, approx 1 year
As assessed by CTCAE V5.0
2 secondary outcomes
Radiological progression free survival
Time frame: Through study completion, approx 1 year
Overall Survival
Time frame: Through study completion, approx 1 year
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 14 Jul 2025.
- Individual participant dataSharing planned: No
Related trials for Uveal Melanoma
RecruitingPhase 2
HS-IT101 Injection Versus Chemotherapy in the Treatment of Advanced Melanoma（FASTIL-Mela02）
Melanoma (Excluding Uveal Melanoma)
Recruiting
Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
Uveal Melanoma
Active, not recruitingObservational study
Choroidal Melanoma Patient-Reported Outcome Study (CM-PRO) in a Subset of AU-011-301 (CoMpass) Subjects
Choroidal Melanoma, Indeterminate Lesions
Active, not recruitingPhase 2
Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal Melanoma
Ciliary Body and Choroid Melanoma, Medium/Large Size, Ciliary Body and Choroid Melanoma, Small Size
RecruitingObservational study
Frequency and Clinical Phenotype of BAP1 Hereditary Predisposition Syndrome
Uveal Melanoma, Cutaneous Melanoma
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.
Anthony Joshua, FRACP principal investigator
St Vincent's Hospital, Sydney
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Aldesleukin in people with Uveal Melanoma and Metastatic Uveal Melanoma, run by St Vincent's Hospital, Sydney at 2 sites in Australia.
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 4 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 14 Jul 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 Australia. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Anthony Joshua, FRACP (61293555655, Anthony.Joshua@svha.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Combination therapy (time frame: Through study completion, approx 1 year). 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 14 Jul 2025.