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

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ClinicalTrials.gov Identifier: NCT02909452
Recruitment Status : Recruiting
First Posted : September 21, 2016
Last Update Posted : February 27, 2017
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Syndax Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
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 Drug: Entinostat Drug: Pembrolizumab Phase 1

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2016
Estimated Primary Completion Date : December 2017
Estimated Study Completion Date : February 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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:
  • SNDX-275
  • MS-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:
  • SNDX-275
  • MS-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:
  • SNDX-275
  • MS-275

Drug: Pembrolizumab
A selective humanized monoclonal antibody (mAb)
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475




Primary Outcome Measures :
  1. 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 ]
  2. Changes from baseline in laboratory results [ Time Frame: Baseline through 90 day safety follow-up visit ]
  3. Changes from baseline in vital signs [ Time Frame: Baseline through 90 day safety follow-up visit ]
  4. Changes from baseline in ECG results [ Time Frame: Baseline through 90 day safety follow-up visit ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab [ Time Frame: Pre-dose through Cycle 3 Day 1 ]
  4. Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab [ Time Frame: Pre-dose through Cycle 3 Day 1 ]
  5. T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab [ Time Frame: Pre-dose through Cycle 3 Day 1 ]
  6. Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab [ Time Frame: Pre-dose through Cycle 3 Day 1 ]

Other Outcome Measures:
  1. 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 ]
  2. Changes in the number of circulating immune related cells [ Time Frame: Pre-dose through Cycle 3 Day 1 ]
  3. Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy [ Time Frame: Pre-dose through Cycle 3 Day 1 ]
  4. Best overall tumor response [ Time Frame: Baseline up to 2 years ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02909452


Contacts
Contact: Sue Fischer 781-795-9419 sfischer@syndax.com
Contact: Anthony Piscitelli 781-795-9426 apiscitelli@syndax.com

Locations
United States, Texas
The START Center for Cancer Care Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez    210-593-5265    isabel.jimenez@start.stoh.com   
Principal Investigator: Anthony W Tolcher, MD         
Sponsors and Collaborators
Syndax Pharmaceuticals
Merck Sharp & Dohme Corp.
Investigators
Study Director: Michael Meyers, MD, PhD Syndax Pharmaceuticals

Responsible Party: Syndax Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02909452     History of Changes
Other Study ID Numbers: SNDX-275-0141
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: February 27, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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.

Keywords provided by Syndax Pharmaceuticals:
entinostat
pembrolizumab
solid tumor
Histone Deacetylase Inhibitor

Additional relevant MeSH terms:
Neoplasms
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Breast Diseases
Digestive System Neoplasms
Gastrointestinal Neoplasms
Neoplasms by Histologic Type
Thoracic Neoplasms
Neoplasms, Glandular and Epithelial
Respiratory Tract Neoplasms
Bronchial Neoplasms
Endocrine Gland Neoplasms
Kidney Neoplasms
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Neoplasms by Site
Skin Diseases
Digestive System Diseases
Gastrointestinal Diseases
Bronchial Diseases
Endocrine System Diseases
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Pembrolizumab
Entinostat
Histone Deacetylase Inhibitors
Antineoplastic Agents