Inclusion Criteria:
1. Metastatic uveal melanoma, confined mainly to the liver, and documented by pathology
review. 2. Serum bilirubin <2 mg/dl, aspartate aminotransferase (AST) and alanine
aminotransferase (ALT) < 5 x upper limit of normal (ULN)
3. Mapping angiogram procedure shows radioembolization is feasible and safe to perform. 4. Human leukocyte antigen-A*02:01(HLA A⁕ 02:01) positive. 5. Patient age ≥ 18 years old. 6. Ability to provide and understand written informed consent. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 8. Patients must have measurable disease or non-measurable disease according to RECIST
1.1 (Eisenhauer et al, 2009).
Exclusion Criteria:
1. Patient with any tumor size > 8 cm. 2. Total bilirubin > 1.5 × ULN, except for patients with Gilbert's syndrome, who are
excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN. 3. Clinical laboratory measurements that meet any of the following criteria:
- - 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 × 109 platelets/L.
4. Angiogram shows vascular shunting which prevents radioembolization. 5. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic
drugs or monoclonal antibodies. 6. 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.
7. 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.
8. 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.
9. Known history of human immunodeficiency virus (HIV) infection. Testing for HIV
status is not necessary unless clinically indicated.
10. 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.
11. 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.
12. 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. 13. 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 (Section 4.9.1):
- - Treatment for well-controlled and asymptomatic adrenal insufficiency, but
replacement dosing is limited to prednisone ≤ 12 mg daily or the equivalent.
- - Local steroid therapies (eg, 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.
14. Patient with morning cortisol < lower limit of normal (unless the participant has
asymptomatic adrenal insufficiency and is receiving stable replacement doses). For
additional information regarding patients with adrenal insufficiency.
15. History of interstitial lung disease. 16. History of pneumonitis that required corticosteroid treatment or current pneumonitis. 17. 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:
- - Managed hypothyroidism (on stable replacement doses)
- Asymptomatic adrenal insufficiency (on stable replacement doses) (For
additional information regarding patients with adrenal insufficiency.
- - Resolved childhood asthma/atopy.
- - Well-controlled asthma.
- - Type I diabetes mellitus.
18. 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)
19. 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. 20. 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. For more information on the timing and
use of hematopoietic colony-stimulating growth factors during study.
21. 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.
22. 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)
23. 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 (defined in Section 4.12), 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. Highly
effective methods of contraception are described in Section 4.12.
24. Male patients must be surgically sterile or use double barrier contraception methods
as described in Section 4.12 from enrollment through treatment and for 6 months
following administration of the last dose of Tebentafusp.
25. Prior radioembolization or other regional, liver-directed therapy, including
chemotherapy or embolization to same site in the liver. 26. Patients with impaired decision-making capacity.
