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

Primary Purpose

Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Entinostat
Pembrolizumab
Sponsored by
Syndax Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasms focused on measuring entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Completed Study SNDX-275-0140 (NCT02897778)
  2. Any AE or toxicity experienced in Study SNDX-275-0140 (NCT02897778) is resolved to less than or equal to Grade 1
  3. Continues to meet inclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study

Exclusion Criteria:

  1. Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study
  2. Continues to meet exclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study

Sites / Locations

  • The START Center for Cancer Care

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

ENT 1mg daily with pembro every 3 weeks

ENT 5mg weekly with pembro every 3 weeks

ENT 10mg bi-weekly with pembro every 3 weeks

Arm Description

Entinostat daily in combination with pembrolizumab every three weeks

Entinostat once weekly in combination with pembrolizumab every three weeks

Entinostat once every other week in combination with pembrolizumab every three weeks

Outcomes

Primary Outcome Measures

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
Changes from baseline in laboratory results
Changes from baseline in vital signs
Changes from baseline in ECG results

Secondary Outcome Measures

AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab
AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab

Full Information

First Posted
September 13, 2016
Last Updated
January 24, 2022
Sponsor
Syndax Pharmaceuticals
Collaborators
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02909452
Brief Title
Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
September 20, 2016 (Actual)
Primary Completion Date
July 17, 2019 (Actual)
Study Completion Date
February 9, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Syndax Pharmaceuticals
Collaborators
Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ENT 1mg daily with pembro every 3 weeks
Arm Type
Active Comparator
Arm Description
Entinostat daily in combination with pembrolizumab every three weeks
Arm Title
ENT 5mg weekly with pembro every 3 weeks
Arm Type
Active Comparator
Arm Description
Entinostat once weekly in combination with pembrolizumab every three weeks
Arm Title
ENT 10mg bi-weekly with pembro every 3 weeks
Arm Type
Active Comparator
Arm Description
Entinostat once every other week in combination with pembrolizumab every three weeks
Intervention Type
Drug
Intervention Name(s)
Entinostat
Other Intervention Name(s)
SNDX-275, MS-275
Intervention Description
HDAC (histone deacetylase) inhibitor
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, MK-3475, SCH-900475
Intervention Description
A selective humanized monoclonal antibody (mAb)
Primary Outcome Measure Information:
Title
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
Time Frame
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
Title
Changes from baseline in laboratory results
Time Frame
Baseline through 90 day safety follow-up visit
Title
Changes from baseline in vital signs
Time Frame
Baseline through 90 day safety follow-up visit
Title
Changes from baseline in ECG results
Time Frame
Baseline through 90 day safety follow-up visit
Secondary Outcome Measure Information:
Title
AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Title
AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Title
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab
Time Frame
Pre-dose through Cycle 3 Day 1
Other Pre-specified Outcome Measures:
Title
Ratio of effector T cells to regulatory T cells in blood pre-therapy and post-therapy
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Changes in the number of circulating immune related cells
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy
Time Frame
Pre-dose through Cycle 3 Day 1
Title
Best overall tumor response
Time Frame
Baseline up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Meyers, MD, PhD
Organizational Affiliation
Syndax Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
The START Center for Cancer Care
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Data will be reviewed throughout the study by the sponsor, clinical research organization assisting with SAE management, and routine monitoring to safeguard the interests of the trial patients and to assess the safety of the interventions administered during the trial.

Learn more about this trial

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

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