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

Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02909452
• Other study ID #: SNDX-275-0141
• Status: Completed
• Phase: Phase 1
• Start date: September 20, 2016
• Est. completion date: February 9, 2021

Study information

• Verified date: June 2018
• Source: Syndax Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: February 9, 2021
• Est. primary completion date: July 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Entinostat
HDAC (histone deacetylase) inhibitor
• Pembrolizumab
A selective humanized monoclonal antibody (mAb)

Locations

Country	Name	City	State
United States	The START Center for Cancer Care	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Syndax Pharmaceuticals	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Ratio of effector T cells to regulatory T cells in blood pre-therapy and post-therapy		Pre-dose through Cycle 3 Day 1
Other	Changes in the number of circulating immune related cells		Pre-dose through Cycle 3 Day 1
Other	Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy		Pre-dose through Cycle 3 Day 1
Other	Best overall tumor response		Baseline up to 2 years
Primary	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
Primary	Changes from baseline in laboratory results		Baseline through 90 day safety follow-up visit
Primary	Changes from baseline in vital signs		Baseline through 90 day safety follow-up visit
Primary	Changes from baseline in ECG results		Baseline through 90 day safety follow-up visit
Secondary	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
Secondary	AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab		Pre-dose through Cycle 3 Day 1
Secondary	Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab		Pre-dose through Cycle 3 Day 1
Secondary	Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab		Pre-dose through Cycle 3 Day 1
Secondary	T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab		Pre-dose through Cycle 3 Day 1
Secondary	Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab		Pre-dose through Cycle 3 Day 1