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

January 24, 2022 updated by: Syndax Pharmaceuticals

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)

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • The START Center for Cancer Care

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: ENT 1mg daily with pembro every 3 weeks
Entinostat daily in combination with pembrolizumab every three weeks
Drug: Entinostat
HDAC (histone deacetylase) inhibitor
Other Names:
  • MS-275
  • SNDX-275
Drug: Pembrolizumab
A selective humanized monoclonal antibody (mAb)
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475
Active Comparator: ENT 5mg weekly with pembro every 3 weeks
Entinostat once weekly in combination with pembrolizumab every three weeks
Drug: Entinostat
HDAC (histone deacetylase) inhibitor
Other Names:
  • MS-275
  • SNDX-275
Drug: Pembrolizumab
A selective humanized monoclonal antibody (mAb)
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475
Active Comparator: ENT 10mg bi-weekly with pembro every 3 weeks
Entinostat once every other week in combination with pembrolizumab every three weeks
Drug: Entinostat
HDAC (histone deacetylase) inhibitor
Other Names:
  • MS-275
  • SNDX-275
Drug: Pembrolizumab
A selective humanized monoclonal antibody (mAb)
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
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
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
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
Time Frame: Baseline through 90 day safety follow-up visit
Baseline through 90 day safety follow-up visit
Changes from baseline in vital signs
Time Frame: Baseline through 90 day safety follow-up visit
Baseline through 90 day safety follow-up visit
Changes from baseline in ECG results
Time Frame: Baseline through 90 day safety follow-up visit
Baseline through 90 day safety follow-up visit

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
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
Pre-dose through Cycle 3 Day 1
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
Pre-dose through Cycle 3 Day 1
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Time Frame
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
Pre-dose through Cycle 3 Day 1
Changes in the number of circulating immune related cells
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1
Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy
Time Frame: Pre-dose through Cycle 3 Day 1
Pre-dose through Cycle 3 Day 1
Best overall tumor response
Time Frame: Baseline up to 2 years
Baseline up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Syndax Pharmaceuticals

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Michael Meyers, MD, PhD, Syndax Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 20, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 17, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 9, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 13, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 25, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SNDX-275-0141

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD 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.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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