Adding IL-2 to Tebentafusp to Eradicate Cancer Progression

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Adding IL-2 to Tebentafusp to Eradicate Cancer Progression

Study Purpose

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: 1. Can combining tebentafusp with IL-2 improve tumor response and overall survival? 2. 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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT07063875
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	St Vincent's Hospital, Sydney
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Anthony Joshua, FRACP
Principal Investigator Affiliation	St Vincent's Hospital, Sydney
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Australia
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Uveal Melanoma, Metastatic Uveal Melanoma, Metastatic Uveal Melanoma in the Liver

Additional Details

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).

Arms & Interventions

Arms

Experimental: Treatment arm

Single arm study -all enrolled participants will receive investigational products- IL-2 (Proleukin) and Tebetafusp

Interventions

Drug: - Aldesleukin

IL-2 in combination with Tebentafusp

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.