Adding IL-2 to tebentafusp to overcome resistance in uveal melanoma
Supplementing With IL-2 to Verifiably eRadicate Radiological Progression
This trial tests whether giving interleukin‑2 (IL‑2) together with tebentafusp can help people with HLA‑A*02:01 metastatic uveal melanoma who progressed on tebentafusp.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 8 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | St Vincent's Hospital, Sydney Academic / other |
| Drugs / interventions | radiation, prednisone |
| Locations | 2 sites (Sydney, New South Wales and 1 other locations) |
| Trial ID | NCT07063875 on ClinicalTrials.gov |
What this trial studies
This phase 1/2 open‑label trial gives all participants combination therapy with IL‑2 and tebentafusp in repeating 28‑day cycles to see if IL‑2 can boost anti‑tumor activity and overcome resistance. Eligible patients are HLA‑A*02:01 positive adults with unresectable or metastatic uveal melanoma and RECIST‑documented progression on single‑agent tebentafusp. The regimen uses short pulses of IL‑2 timed around scheduled tebentafusp doses, with close safety monitoring and predefined criteria for dose modifications. Key endpoints include safety and response rates, with overall survival and progression‑free survival as important secondary measures.
Who should consider this trial
Good fit: Ideal candidates are HLA‑A*02:01 positive adults with unresectable or metastatic uveal melanoma, ECOG 0–1, and RECIST‑documented progression on single‑agent tebentafusp without untreated CNS disease.
Not a fit: Patients who are HLA‑A*02:01 negative, have untreated or symptomatic CNS metastases, poor performance status, or recent systemic immunosuppression are unlikely to be eligible or to benefit.
Why it matters
Potential benefit: If successful, the combination could increase tumor shrinkage and extend survival for patients who developed resistance to tebentafusp.
How similar studies have performed: Tebentafusp has previously shown a survival benefit in HLA‑A*02:01 metastatic uveal melanoma, but combining it with IL‑2 is a novel approach with limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Histologically or cytologically confirmed metastatic UM or unresectable UM patients 2. HLA-A\*02:01 positive 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 4. RECIST 1.1 defined progression on single-agent Tebentafusp, with no other intervening systemic therapies Exclusion Criteria: 1. 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) 2. 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. 3. 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. 4. 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.
Where this trial is running
Sydney, New South Wales and 1 other locations
- Kinghorn Cancer Centre, St. Vincent's Hospital — Sydney, New South Wales, Australia (Recruiting)
- Alfred Hospital — Melbourne, Victoria, Australia (Not_yet_recruiting)
Study contacts
- Principal investigator: Anthony Joshua, FRACP — St Vincent's Hospital, Sydney
- Study coordinator: Anthony Joshua, FRACP
- Email: Anthony.Joshua@svha.org.au
- Phone: 61293555655
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.