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

Phase 1

Completed

• Conditions: Neoplasms by Histologic Type; Respiratory Tract Neoplasms; Endocrine Gland Neoplasms; Breast Diseases; Lung Neoplasms; Lung Diseases; Renal Neoplasm; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Solid Tumors
• Interventions: Drug: Entinostat; Drug: Pembrolizumab

• Registration Number: NCT02909452
• Lead Sponsor: 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

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 Timeline

• Study First Submitted: 2016-09-13
• Study First Submitted QC: 2016-09-16
• Study Start: 2016-09-20
• Study First Posted: 2016-09-21
• Status Verified: 2018-06
• Primary Completion: 2019-07-17
• Study Completion: 2021-02-09
• Last Update Submitted: 2022-01-24
• Last Update Posted: 2022-01-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ENT 5mg weekly with pembro every 3 weeks	Entinostat	Entinostat once weekly in combination with pembrolizumab every three weeks
ENT 1mg daily with pembro every 3 weeks	Pembrolizumab	Entinostat daily in combination with pembrolizumab every three weeks
ENT 10mg bi-weekly with pembro every 3 weeks	Entinostat	Entinostat once every other week in combination with pembrolizumab every three weeks
ENT 1mg daily with pembro every 3 weeks	Entinostat	Entinostat daily in combination with pembrolizumab every three weeks
ENT 5mg weekly with pembro every 3 weeks	Pembrolizumab	Entinostat once weekly in combination with pembrolizumab every three weeks
ENT 10mg bi-weekly with pembro every 3 weeks	Pembrolizumab	Entinostat once every other week in combination with pembrolizumab every three weeks

Primary Outcome Measures

Name	Time	Method
Changes from baseline in laboratory results	Baseline through 90 day safety follow-up visit
Changes from baseline in vital signs	Baseline through 90 day safety follow-up visit
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
Changes from baseline in ECG results	Baseline through 90 day safety follow-up visit

Secondary Outcome Measures

Name	Time	Method
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
AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab	Pre-dose through Cycle 3 Day 1
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab	Pre-dose through Cycle 3 Day 1
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab	Pre-dose through Cycle 3 Day 1
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab	Pre-dose through Cycle 3 Day 1
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab	Pre-dose through Cycle 3 Day 1

Trial Locations

Locations (1)

The START Center for Cancer Care; 🇺🇸 San Antonio, Texas, United States