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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Uveal Melanoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Entinostat

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Västra Götaland Region
    • Gothenburg, Västra Götaland Region, Sweden, SE-413 45
      • Department of Oncology, Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vastra Gotaland Region
• Collaborators: Merck Sharp & Dohme LLC; Syndax Pharmaceuticals

Publications and helpful links

General Publications

• 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.
• Sah VR, Jespersen H, Karlsson J, Nilsson LM, Bergqvist M, Johansson I, Carneiro A, Helgadottir H, Levin M, Ullenhag G, Stahlberg A, Olofsson Bagge R, Nilsson JA, Ny L. Chemokine Analysis in Patients with Metastatic Uveal Melanoma Suggests a Role for CCL21 Signaling in Combined Epigenetic Therapy and Checkpoint Immunotherapy. Cancer Res Commun. 2023 May 18;3(5):884-895. doi: 10.1158/2767-9764.CRC-22-0490. eCollection 2023 May.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2018
• Primary Completion (Actual): January 31, 2023
• Study Completion (Actual): January 31, 2023

Study Registration Dates

• First Submitted: February 22, 2016
• First Submitted That Met QC Criteria: February 26, 2016
• First Posted (Estimated): March 3, 2016

Study Record Updates

• Last Update Posted (Actual): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Uveal melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Eye Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Uveal Diseases; Neuroendocrine Tumors; Nevi and Melanomas; Eye Neoplasms; Melanoma; Uveal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Histone Deacetylase Inhibitors; Pembrolizumab; Entinostat
• Other Study ID Numbers: 2016-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No