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

Metastatic Uveal Melanoma Clinical Trial

— PEMDAC  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02697630
• Other study ID #: 2016-1
• Status: Completed
• Phase: Phase 2
• Start date: February 21, 2018
• Est. completion date: January 31, 2023

Study information

• Verified date: December 2023
• Source: Vastra Gotaland Region
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: January 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Melanoma
• Metastatic Uveal Melanoma
• Uveal Neoplasms

Intervention

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

Locations

Country	Name	City	State
Sweden	Department of oncology, Sahlgrenska University Hospital	Gothenburg	Västra Götaland Region

Sponsors (3)

Lead Sponsor	Collaborator
Vastra Gotaland Region	Merck Sharp & Dohme LLC, Syndax Pharmaceuticals

Country where clinical trial is conducted

Sweden, 

References & Publications (3)

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 mel — View Citation

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 pembrolizum — View Citation

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 — View Citation

Outcome

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