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

• ClinicalTrials.gov Identifier: NCT02697630
• Recruitment Status: Completed
• First Posted: March 3, 2016
• Last Update Posted: December 8, 2023
• Sponsor: Vastra Gotaland Region
• Collaborators: Merck Sharp & Dohme LLC; Syndax Pharmaceuticals
• Information provided by (Responsible Party): Vastra Gotaland Region

Tracking Information

• First Submitted Date: February 22, 2016
• First Posted Date: March 3, 2016
• Last Update Posted Date: December 8, 2023
• Actual Study Start Date: February 21, 2018
• Actual Primary Completion Date: January 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 26, 2016)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 25, 2016)

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

Original Secondary Outcome Measures (submitted: February 26, 2016)

• Clinical benefit rate (CBR) [ Time Frame: 18 weeks from first dose ]
• Progression free survival (PFS) [ Time Frame: From first dose up to 24 months ]
• Overall Survival (OS) [ Time Frame: From first dose up to 24 months ]
• Objective Response Rate (ORR) in subgroups determined by cell death-ligand 1 (PD-L1) expression [ Time Frame: From first dose up to 24 months ]
• Objective Response Rate (ORR) in subgroups determined by serum Lactate dehydrogenase (LDH) level [ Time Frame: From first dose up to 24 months ]
• Objective Response Rate (ORR) in subgroups determined by Guanine Nucleotide-binding Protein G (q) subunit alpha/ Guanine Nucleotide-binding Protein G subunit alpha-11 (GNAQ)/(GNA11) mutation status [ Time Frame: From first dose up to 24 months ]
• Objective Response Rate (ORR) in subgroups determined by the presence of non-hepatic metastases. [ Time Frame: From first dose up to 24 months ]
• Best overall response (BOR) [ Time Frame: From first dose up to 24 months ]
• Time To Response (TTR) [ Time Frame: From first dose up to 24 months ]
• Duration of objective response (DOR) [ Time Frame: From first dose up to 24 months ]
• Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: From first dose up to 24 months ]
  Incidence and severity
• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) [ Time Frame: 18 weeks from first dose ]
• Quality of Life (QoL) assessed by FACT-G [ Time Frame: From first dose up to 24 months ]
• Quality of Life (QoL) assessed by EQ5D-3L [ Time Frame: From first dose up to 24 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy Study of Pembrolizumab With Entinostat to Treat Metastatic Melanoma of the Eye
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Uveal Melanoma

Intervention

• 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

Study Arms

Experimental: Pembrolizumab and Entinostat

Interventions:

• Drug: Pembrolizumab
• Drug: Entinostat

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 25, 2016): 29
• Original Estimated Enrollment (submitted: February 26, 2016): 24
• Actual Study Completion Date: January 31, 2023
• Actual Primary Completion Date: January 31, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT02697630
• Other Study ID Numbers: 2016-1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Vastra Gotaland Region
• Original Responsible Party: Same as current
• Current Study Sponsor: Vastra Gotaland Region
• Original Study Sponsor: Same as current

Collaborators

• Merck Sharp & Dohme LLC
• Syndax Pharmaceuticals

• Investigators: Not Provided
• PRS Account: Vastra Gotaland Region
• Verification Date: December 2023