Efficacy Study of Pembrolizumab With Entinostat to Treat Metastatic Melanoma of the Eye

Study Overview
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Brief Summary
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The purpose of this study is to see if the combination of entinostat and pembrolizumab can be an effective treatment for patients with melanoma of the eye (uveal melanoma) that has spread to other sites of the body (metastatic disease). Pembrolizumab is an antibody that helps the immune system to attack cancer cells. Although pembrolizumab has proven clinical efficacy in treating patients with metastatic cutaneous melanoma, an effect on metastatic uveal melanoma has not been established. Entinostat is a histone deacetylase (HDAC) inhibitor that has effects on both cancer cells and immune regulatory cells, thus potentially enhancing the effects of immunotherapy.

Official Title
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A Multicenter Phase II Open Label Study to Evaluate Efficacy of Concomitant Use of Pembrolizumab and Entinostat in Adult Patients With Metastatic Uveal Melanoma

Conditions
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Metastatic Uveal Melanoma

Intervention / Treatment
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* Drug: Pembrolizumab
* Drug: Entinostat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age above 18 years. Signed and dated written informed consent before the start of specific protocol procedures. ECOG PS 0-1 Histologically/cytologically confirmed stage IV uveal melanoma Measurable disease by computed tomography (CT) or Magnetic Resonance Imaging (MRI) per RECIST 1.1 criteria Any number of prior therapies (including none), with the exception of anticancer immunotherapy Exclusion Criteria: Active brain metastases (symptomatic and/or requiring corticosteroids) or leptomeningeal metastases Previous treatment with anticancer immunotherapy Pregnant or nursing (lactating) women Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study Active autoimmune disease Immune deficiency or treatment with systemic corticosteroids Use of other investigational drugs (drugs not marketed for any indication) within 28 days before study drug administration Life expectancy of less than 3 months

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: Pembrolizumab and Entinostat<br> | Drug: Pembrolizumab<br>* 200 mg administered intravenously (IV) every third week until progression or unacceptable toxicity for a maximum of 24 months<br>Drug: Entinostat<br>* 5 mg by mouth (PO) once weekly until progression or unacceptable toxicity for a maximum of 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | The proportion of patients that have a best overall response of complete response (CR) or partial response (PR), as assessed by RECIST 1.1. | From first dose up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit rate (CBR) |  | 18 weeks from first dose | 
| Progression free survival (PFS) |  | From first dose up to 24 months | 
| Overall Survival (OS) |  | From first dose up to 24 months | 
| Best overall response (BOR) |  | From first dose up to 24 months | 
| Time To Response (TTR) |  | From first dose up to 24 months | 
| Duration of objective response (DOR) |  | From first dose up to 24 months | 
| Adverse Events (AEs) and Serious Adverse Events (SAEs). | Incidence and severity | From first dose up to 24 months | 
| Eastern Cooperative Oncology Group (ECOG) Performance status (PS) |  | 18 weeks from first dose | 
| Quality of Life (QoL) assessed by FACT-G |  | From first dose up to 24 months | 
| Quality of Life (QoL) assessed by EQ5D-3L |  | From first dose up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveal melanoma