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

NCT02697630 | Completed Phase 2

• 1 other identifier: 2016-1
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Uveal Melanoma

Keywords

Uveal melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• 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

Study Arms (1)

Pembrolizumab and Entinostat

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Entinostat

Interventions

Pembrolizumab DRUG

200 mg administered intravenously (IV) every third week until progression or unacceptable toxicity for a maximum of 24 months

Pembrolizumab and Entinostat

Entinostat DRUG

5 mg by mouth (PO) once weekly until progression or unacceptable toxicity for a maximum of 24 months

Pembrolizumab and Entinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead
• Merck Sharp & Dohme LLC: collaborator
• Syndax Pharmaceuticals: collaborator

Study Sites (1)

Department of oncology, Sahlgrenska University Hospital

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

Location

Related Publications (3)

• 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.

  PMID: 34453044 RESULT

• 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.

  PMID: 37377898 RESULT

• 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.

  PMID: 31046743 RESULT

MeSH Terms

Conditions

Uveal Melanoma

Interventions

pembrolizumab; entinostat

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2016
• First Posted: March 3, 2016
• Study Start: February 21, 2018
• Primary Completion: January 31, 2023
• Study Completion: January 31, 2023
• Last Updated: December 8, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)