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

• Sponsor: Syndax Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02909452
• Collaborator: Merck Sharp & Dohme LLC (Industry)
• Enrollment: 30
• Location: 1
• Arms: 3
• Actual Duration (Months): 52.7
• Patients Per Site Per Month: 0.6

Study Details

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

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 Design

• Study Type: Interventional
• Actual 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)
• Actual Study Start Date: Sep 20, 2016
• Actual Primary Completion Date: Jul 17, 2019
• Actual Study Completion Date: Feb 9, 2021

Arms and Interventions

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

Outcome Measures

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 [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 [Baseline through 90 day safety follow-up visit]

3. Changes from baseline in vital signs [Baseline through 90 day safety follow-up visit]

4. Changes from baseline in ECG results [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 [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 [Pre-dose through Cycle 3 Day 1]

3. Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab [Pre-dose through Cycle 3 Day 1]

4. Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab [Pre-dose through Cycle 3 Day 1]

5. T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab [Pre-dose through Cycle 3 Day 1]

6. Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab [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 [Pre-dose through Cycle 3 Day 1]

2. Changes in the number of circulating immune related cells [Pre-dose through Cycle 3 Day 1]

3. Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy [Pre-dose through Cycle 3 Day 1]

4. Best overall tumor response [Baseline up to 2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The START Center for Cancer Care	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Syndax Pharmaceuticals
• Merck Sharp & Dohme LLC

Investigators

• Study Director: Michael Meyers, MD, PhD, Syndax Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Syndax Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02909452
• Other Study ID Numbers: SNDX-275-0141
• First Posted: Sep 21, 2016
• Last Update Posted: Jan 25, 2022
• Last Verified: Jun 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Syndax Pharmaceuticals: entinostat; pembrolizumab; solid tumor; Histone Deacetylase Inhibitor
• Additional relevant MeSH terms: Neoplasms; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; 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; Lung Diseases; Breast Diseases; Pembrolizumab; Entinostat

Study Results

No Results Posted as of Jan 25, 2022