Clinical trial NCT02697630: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Uveal Melanoma
Keywords: Uveal melanoma
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
name: Syndax Pharmaceuticals
First posted: 2016-03-03
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose up to 24 months
Secondary outcomes:
measure: Clinical benefit rate (CBR)
timeFrame: 18 weeks from first dose
measure: Progression free survival (PFS)
timeFrame: From first dose up to 24 months
measure: Overall Survival (OS)
timeFrame: From first dose up to 24 months
measure: Best overall response (BOR)
timeFrame: From first dose up to 24 months
measure: Time To Response (TTR)
timeFrame: From first dose up to 24 months
measure: Duration of objective response (DOR)
timeFrame: From first dose up to 24 months
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs).
timeFrame: From first dose up to 24 months
measure: Eastern Cooperative Oncology Group (ECOG) Performance status (PS)
timeFrame: 18 weeks from first dose
measure: Quality of Life (QoL) assessed by FACT-G
timeFrame: From first dose up to 24 months
measure: Quality of Life (QoL) assessed by EQ5D-3L
timeFrame: From first dose up to 24 months
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of oncology, Sahlgrenska University Hospital
state: Västra Götaland Region
Study officials:
References:
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 pembrolizumab and entinostat in patients with metastatic uveal melanoma. Nat Commun. 2021 Aug 27;12(1):5155. doi: 10.1038/s41467-021-25332-w.
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 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.
citation: 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.