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

• ClinicalTrials.gov Identifier: NCT02697630
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2016
• Last Update Posted: October 16, 2019
• Sponsor: Vastra Gotaland Region
• Collaborators: Merck Sharp & Dohme LLC; Syndax Pharmaceuticals
• Information provided by (Responsible Party): Vastra Gotaland Region

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Metastatic Uveal Melanoma	Drug: Pembrolizumab; Drug: Entinostat	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Open Label Study to Evaluate Efficacy of Concomitant Use of Pembrolizumab and Entinostat in Adult Patients With Metastatic Uveal Melanoma
• Actual Study Start Date: February 21, 2018
• Estimated Primary Completion Date: August 2021
• Estimated Study Completion Date: August 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab and Entinostat	Drug: Pembrolizumab; 200 mg administered intravenously (IV) every third week until progression or unacceptable toxicity for a maximum of 24 months; Drug: Entinostat; 5 mg by mouth (PO) once weekly until progression or unacceptable toxicity for a maximum of 24 months

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Sweden

Department of oncology, Sahlgrenska University Hospital

Gothenburg, Västra Götaland Region, Sweden, SE-413 45

Sponsors and Collaborators

Vastra Gotaland Region

Merck Sharp & Dohme LLC

Syndax Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ny L, Jespersen H, Karlsson J, Alsen S, Filges S, All-Eriksson C, Andersson B, Carneiro A, Helgadottir H, Levin M, Ljuslinder I, Olofsson Bagge R, Sah VR, Stierner U, Stahlberg A, Ullenhag G, Nilsson LM, Nilsson JA. The PEMDAC phase 2 study of pembrolizumab and entinostat in patients with metastatic uveal melanoma. Nat Commun. 2021 Aug 27;12(1):5155. doi: 10.1038/s41467-021-25332-w.

Jespersen H, Olofsson Bagge R, Ullenhag G, Carneiro A, Helgadottir H, Ljuslinder I, Levin M, All-Eriksson C, Andersson B, Stierner U, Nilsson LM, Nilsson JA, Ny L. Concomitant use of pembrolizumab and entinostat in adult patients with metastatic uveal melanoma (PEMDAC study): protocol for a multicenter phase II open label study. BMC Cancer. 2019 May 2;19(1):415. doi: 10.1186/s12885-019-5623-3.

• Responsible Party: Vastra Gotaland Region
• ClinicalTrials.gov Identifier: NCT02697630
• Other Study ID Numbers: 2016-1
• First Posted: March 3, 2016
• Last Update Posted: October 16, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Vastra Gotaland Region:

Uveal melanoma

Additional relevant MeSH terms:

Uveal Neoplasms; Uveal Diseases; Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Pembrolizumab; Entinostat; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action; Histone Deacetylase Inhibitors; Enzyme Inhibitors