Uveal Melanoma, Metastatic
Conditions
Keywords
Tebentafusp, Dexamethasone, Cytokine release syndrome, Prophylaxis
Brief summary
The goal of this clinical trial is to learn if a low dose of dexamethasone can prevent cytokine release syndrome in participants treated with tebentafusp for advanced uveal melanoma. The main questions the study aims to answer are: How many participants get cytokine release syndrome? How severe is the cytokine release syndrome? What other side effects happen due to dexamethasone and/or tebentafusp? Participants will be treated with tebentafusp per standard practices. For this study, participants will receive dexamethasone before infusion of the first 4 doses of tebentafusp. Participants will have visits for checkups and tests at the time they are given the medications and 9 weeks after they started. Other visits will be approximately every 6 months for at least 2 years and can be done in person or remotely (telehealth).
Detailed description
This is a single-arm multi-site phase II study of prophylactic low-dose dexamethasone premedication in patients receiving tebentafusp per standard of care for HLA-A\*02:01-positive advanced uveal melanoma. Dexamethasone doses (2 and 4 mg) will be tested sequentially per a Simon's optimal two-stage design. Tebentafusp is a first-in-class, bispecific gp100 peptide and CD3 T-cell engager shown to improve overall survival of HLA-A\*02:01-positive patients with untreated, advanced uveal melanoma. The most common treatment-related adverse event associated with tebentafusp is cytokine release syndrome. Given the significant patient and health system burden of cytokine release syndrome in tebentafusp-treated patients, the investigators plan to use prophylactic low-dose dexamethasone premedication. The investigators hypothesize that this strategy will decrease the incidence and severity of cytokine release syndrome. Improvements in the safety and tolerability of tebentafusp could enable broader use of tebentafusp in outpatient and community settings and reduce hospitalization-related costs and barriers to care.
Interventions
DRUGDexamethasone
Prophylactic low-dose dexamethasone premedication
Sponsors
University of California, San Diego
Immunocore Ltd
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Simon two-stage design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Age ≥18 years. 4. Histologically confirmed advanced uveal melanoma. 5. HLA-A\*02:01 positive as determined per standard of care before enrollment in the study. 6. Planned treatment with tebentafusp as first-line systemic therapy for advanced uveal melanoma per standard of care. 7. For participants able to become pregnant: use of highly effective contraception for at least 4 weeks prior to initiation of tebentafusp and agreement to use such a method for duration of tebentafusp treatment until 6 months after the last dose of tebentafusp. 8. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner from trial initiation and for duration of tebentafusp treatment until 6 months after the last dose of tebentafusp.
Exclusion criteria
1. Use of systemic corticosteroid (including hydrocortisone) within 3 weeks of study entry. 2. Pregnancy or lactation. 3. Known severe hypersensitivity reaction to monoclonal antibodies or biologics.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade ≥2 cytokine release syndrome | During the first 4 doses of tebentafusp treatment (fourth dose is on day 22) | Proportion of participants with grade ≥2 cytokine release syndrome |
Countries
United States
Contacts
CONTACTSoo Park, MD
CONTACTSkin Research Team
PRINCIPAL_INVESTIGATORSoo Park, MD
University of California, San Diego
Outcome results
None listed