A Study of Concurrent Stereotactic Body Radiotherapy With Opdualag in Metastatic Uveal Melanoma

Study Overview
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Brief Summary
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This is a phase 2 trial of concurrent stereotactic radiation therapy (SBRT) with immunotherapy with relatlimab and nivolumab for up to two years. SBRT will be given in three doses of 15Gy each to 1-5 separate metastases. Opdualag (nivolumab 480mg and relatlimab 160mg) will be given every 4 weeks for two years

Detailed Description
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Metastatic uveal melanoma has no standard therapy, but there is evidence that both radiation therapy and immunotherapy may be helpful and may be synergistic. This is a phase 2 trial of concurrent stereotactic radiation therapy (SBRT) with immunotherapy with Opdualag (nivolumab 480mg and relatlimab 160mg) for up to two years. SBRT will be given in three doses of 15Gy each to 1-5 separate metastases, limiting the total dosage to 700cc's of normal liver to <15Gy. Opdualag (nivolumab 480mg and relatlimab 160mg) will be given every 4 weeks for two years. Objectives are to determine the safety and tolerability, and iRECIST will be used to determine responses.We will treat up to 50 patients.

Official Title
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A Phase II Study of Concurrent Stereotactic Body Radiotherapy With Relatlimab and Nivolumab in Patients With Metastatic Uveal Melanoma

Conditions
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Uveal Melanoma

Intervention / Treatment
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* Radiation: stereotactic body radiotherapy
* Drug: Immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: measurable metastatic uveal melanoma. No concomitant therapy. Prior PD1 or tebendafesp allowed. Performance status 0-1. No active Hepatitis B. No known HIV infection. WBC>2000, ANC>1500, Hgb >8. Creatinine < 3 x ULN. AST & ALT < 2.5 x ULN Bilirubin < 2 x ULN. Albumin >2.9 Exclusion Criteria: Liver tumor volume > 50%. Active CNS metastases. Pregnancy. Prior therapy with Opdualag or relatlimab Certain autoimmune diseases. Previous liver embolization or radiation. Use of systemic steroids

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: one arm<br>see below | Radiation: stereotactic body radiotherapy<br>* Stereotactic Body radiotherapy will be given to 1-5 target metastases in 3 doses over 8 days or less. Each dose will be 15Gy for a total dose of 45GY<br>Drug: Immunotherapy<br>* Opdualag (nivolumab 480mg and relatlimab 160mg) will be given every 4 weeks for two years<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety and tolerability of the therapy | toxicity measured by CTAE graded 3-5 toxicities | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | iRECIST defined response rates | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic