Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The objectives of this study are to explore different dosing levels and schedules of entinostat in combination with pembrolizumab in patients with advanced solid tumors, in terms of safety, tolerability, pharmacokinetics (PK), impact on immune correlatives, and efficacy

Detailed Description
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This is a Phase 1, open-label, single center, randomized study to assess the safety and tolerability of 3 different dose regimens of entinostat in combination with pembrolizumab in patients with advanced solid tumors who previously completed Study SNDX-275-0140 (NCT02897778). Up to 30 patients will be randomized in a 1:1:1 fashion to one of three arms. In the event that greater than or equal to 2 out of the first 6 patients randomized experience a dose-limiting toxicity, the next patient randomized to that Arm will receive treatment at a reduced starting dose as outlined in the protocol.

Official Title
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A Phase 1, Randomized, Open-Label, Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors (SNDX-275-0141, MK3475-460/KEYNOTE-460)

Conditions
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Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Digestive System Neoplasms, Endocrine Gland Neoplasms, Carcinoma, Non-Small-Cell Lung, Lung Diseases, Breast Diseases, Renal Neoplasm, Solid Tumors

Intervention / Treatment
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* Drug: Entinostat
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed Study SNDX-275-0140 (NCT02897778) Any AE or toxicity experienced in Study SNDX-275-0140 (NCT02897778) is resolved to less than or equal to Grade 1 Continues to meet inclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study Exclusion Criteria: Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study Continues to meet exclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ENT 1mg daily with pembro every 3 weeks<br>Entinostat daily in combination with pembrolizumab every three weeks | Drug: Entinostat<br>* HDAC (histone deacetylase) inhibitor<br>* Other names: MS-275;Drug: Pembrolizumab<br>* A selective humanized monoclonal antibody (mAb)<br>* Other names: SCH-900475;|
| Active Comparator: ENT 5mg weekly with pembro every 3 weeks<br>Entinostat once weekly in combination with pembrolizumab every three weeks | Drug: Entinostat<br>* HDAC (histone deacetylase) inhibitor<br>* Other names: MS-275;Drug: Pembrolizumab<br>* A selective humanized monoclonal antibody (mAb)<br>* Other names: SCH-900475;|
| Active Comparator: ENT 10mg bi-weekly with pembro every 3 weeks<br>Entinostat once every other week in combination with pembrolizumab every three weeks | Drug: Entinostat<br>* HDAC (histone deacetylase) inhibitor<br>* Other names: MS-275;Drug: Pembrolizumab<br>* A selective humanized monoclonal antibody (mAb)<br>* Other names: SCH-900475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) resulting in the permanent discontinuation of study drug, and deaths occurring within the reporting period required for the study |  | Each treatment cycle is 21 days. All events will be collected from informed consent through 90 days post-last dose or through 30 days after initiation of new anti-cancer therapy | 
| Changes from baseline in laboratory results |  | Baseline through 90 day safety follow-up visit | 
| Changes from baseline in vital signs |  | Baseline through 90 day safety follow-up visit | 
| Changes from baseline in ECG results |  | Baseline through 90 day safety follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 
| AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 
| Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 
| Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 
| T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 
| Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab |  | Pre-dose through Cycle 3 Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor