Immunotherapy (Tebentafusp) and Radiation Therapy (Yttrium-90 Radioembolization) for the Treatment of Uveal Melanoma Metastatic to the Liver
This phase II trial studies the safety and side effects of tebentafusp in combination with yttrium-90 (Y-90) radioembolization, and how well they work in treating patients with uveal melanoma that has spread from where it first started to the liver (metastatic). Tebentafusp works by attracting specific types of cells called T-cells to abnormal cells. T-cells are part of the body’s immune system, which help fight infections and can also find and kill abnormal cells. However, abnormal cells that have become cancerous find ways to shut down the immune system’s defenses. Tebentafusp may help T-cells find and attack uveal melanoma cells. Y-90 radioembolization is a type of radiation therapy used for patients with tumors in the liver. During this procedure, microscopic glass beads containing yttrium-90, a radioactive element, are inserted into liver tumors using a thin, flexible tube called a catheter. The radioactivity emitted from the glass beads directly injures and kills uveal melanoma tumor cells in the liver and may also activate the body’s immune systems to find and attack other uveal melanoma cells in the body. Tebentafusp in combination with Y-90 radioembolization may be safe and effective in treating uveal melanoma metastatic to the liver.
Inclusion Criteria
- Metastatic uveal melanoma, confined mainly to the liver, and documented by pathology review
- Serum bilirubin < 2 mg/dl
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
- Mapping angiogram procedure shows radioembolization is feasible and safe to perform
- Human leukocyte antigen-A*02:01(HLA A* 02:01) positive
- Patient age ≥ 18 years old
- Ability to provide and understand written informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status 0–1
- Patients must have measurable disease or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Eisenhauer et al, 2009)
Exclusion Criteria
- Patient with any tumor size > 8 cm
- Total bilirubin > 1.5 × upper limit of normal (ULN), except for patients with Gilbert’s syndrome, who are excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN
- Alanine aminotransferase (ALT) > 3 × ULN
- Aspartate aminotransferase (AST) > 3 × ULN
- Absolute neutrophil count (ANC) < 1.0 × 10^9 cells/L
- Absolute lymphocyte count < 0.5 × 10^9 cells/L
- Platelet count < 75 × 10^9 platelets/L
- Hemoglobin < 8 g/dL
- Angiogram shows vascular shunting which prevents radioembolization
- History of severe hypersensitivity reactions (e.g., anaphylaxis) to other biologic drugs or monoclonal antibodies
- Patients with clinically significant cardiac disease or impaired cardiac function, including any of the following: * Congestive heart failure (New York Heart Association Class ≥ 3) * Uncontrolled hypertension (consistent findings of systolic blood pressure [BP] > 160 mmHg or diastolic BP > 110 mmHg) * History of ventricular arrhythmia currently requiring medical treatment * Uncontrolled atrial fibrillation * Electrocardiogram (ECG) QT interval corrected for heart rate by Fridericia's method (QTcF) > 470 msec during screening obtained on triplicate ECGs or known history of congenital prolonged QT syndrome * Acute myocardial infarction or unstable angina pectoris ≤ 6 months prior to screening
- Presence of symptomatic or untreated central nervous system (CNS) metastases or CNS metastases that require doses of corticosteroids within 14 days prior to study treatment Day 1
- Active infection requiring systemic antibiotic therapy. Patients requiring systemic antibiotics for infection must have completed therapy at least 1 week prior to the first dose of tebentafusp
- Known history of human immunodeficiency virus (HIV) infection. Testing for HIV status is not necessary unless clinically indicated
- Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the patient has a history of HBV or HCV infection
- Malignant disease other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type.
- Any medical condition that would, in the Investigator’s or Sponsor’s judgment, prevent the patient’s participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results
- Patients who received systemic treatment with steroids or any other immunosuppressive drug within 2 weeks of the planned first dose of study intervention. The following exceptions are permitted: * Treatment for well-controlled and asymptomatic adrenal insufficiency, but replacement dosing is limited to prednisone ≤ 12 mg daily or the equivalent * Local steroid therapies (e.g., optic, ophthalmic, intra-articular, or inhaled medications) * Premedication for allergy to contrast reagent * Steroids for management of CNS metastases > 14 days prior to the planned first dose of study intervention * To treat asthma or chronic obstructive pulmonary disease exacerbations > 14 days prior to the planned first dose of study intervention (only short-term oral or IV use in doses > 12 mg/day prednisone equivalent) * For inhalation in the management of asthma or chronic obstructive pulmonary disease * Any premedications required per protocol
- Patient with morning cortisol < lower limit of normal (unless the participant has asymptomatic adrenal insufficiency and is receiving stable replacement doses)
- History of interstitial lung disease
- History of pneumonitis that required corticosteroid treatment or current pneumonitis
- Patients with active autoimmune disease requiring immunosuppressive treatment, including inflammatory bowel disease (ulcerative colitis or Crohn’s disease), within 2 years of screening * NOTE: The following exceptions are permitted: ** Vitiligo ** Alopecia ** Managed hypothyroidism (on stable replacement doses) ** Asymptomatic adrenal insufficiency (on stable replacement doses) ** Psoriasis ** Resolved childhood asthma/atopy ** Well-controlled asthma ** Type I diabetes mellitus
- Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary)
- Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass
- Use of hematopoietic colony-stimulating growth factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage colony-stimulating factor [M-CSF]) ≤ 3 weeks prior to start of tebentafusp. An erythroid-stimulating agent is allowed as long as it was initiated at least 3 weeks prior to the first dose of study treatment and the patient is not red blood cell (RBC) transfusion dependent
- Patient receiving a live or attenuated vaccine(s) ≤ 28 days prior to the first dose of study intervention * NOTE: Non-live vaccines (including adenoviral and messenger ribonucleic acid [mRNA]-based coronavirus disease-2019 [COVID-19] vaccines) are allowed but are not to be administered for at least 2 weeks before and 3 weeks after start of study treatment and within 24 hours before or after study treatment administration following the first 3 weeks of study treatment
- Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as the state of a female after conception and until the termination of gestation)
- Women of childbearing potential (WoCBP) who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment, and must agree to continue using such precautions for 6 months after the final dose of tebentafusp; cessation of birth control after this point should be discussed with a responsible physician
- Male patients must be surgically sterile or use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of tebentafusp
- Prior radioembolization or other regional, liver-directed therapy, including chemotherapy or embolization to same site in the liver
- Patients with impaired decision-making capacity
Additional locations may be listed on ClinicalTrials.gov for NCT06627244.
Locations matching your search criteria
United States
Florida
Aventura
Coral Gables
Coral Springs
Deerfield Beach
Hollywood
Miami
Plantation
PRIMARY OBJECTIVE:
I. Assess treatment-related tolerability, toxicity, and efficacy of the combination of tebentafusp and radioembolization in patients with metastatic uveal melanoma involving the liver.
SECONDARY OBJECTIVE:
I. Assess disease control rate (DCR), overall response rate (ORR), duration of response (DOR), and overall survival (OS).
EXPLORATORY OBJECTIVES:
I. Assess biomarkers which may predict response.
II. To describe tumor and normal tissue absorbed radioembolization dose and its relationship with liver volume changes after treatment and DCR, progression free survival (PFS), and OS.
III. Baseline radiomic and delta-radiomic analyses of diagnostic imaging and bremsstrahlung single-photon emission computed tomography/computed tomography (SPECT/CT) for correlation with clinical outcomes (DCR, PFS, and OS).
OUTLINE:
Patients undergo mapping angiography that consists of technetium Tc-99m albumin aggregated (99mTc-MAA) given via intra-arterial injection and a SPECT/CT scan on study. Patients then undergo trans-arterial radioembolization (TARE) by receiving yttrium Y 90 glass microspheres via intra-arterial injection over < 5 minutes on study. Beginning between 14 and 28 days after TARE, patients receive tebentafusp intravenously (IV) over 15-20 minutes on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or magnetic resonance imaging (MRI) and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days and then once every 12 weeks for 1 year.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUniversity of Miami Miller School of Medicine-Sylvester Cancer Center
Principal InvestigatorLynn G. Feun
- Primary ID20231324
- Secondary IDsNCI-2025-00070
- ClinicalTrials.gov IDNCT06627244