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

NCT02909452 | Completed Phase 1

• 1 other identifier: SNDX-275-0141
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

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

Keywords

entinostat; pembrolizumab; solid tumor; Histone Deacetylase Inhibitor

Outcome Measures

Primary Outcomes (4)

• 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 laboratory results

  Baseline through 90 day safety follow-up visit

• Changes from baseline in vital signs

  Baseline through 90 day safety follow-up visit

• Changes from baseline in ECG results

  Baseline through 90 day safety follow-up visit

Secondary Outcomes (6)

• 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

• T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab

  Pre-dose through Cycle 3 Day 1

Other Outcomes (4)

• Ratio of effector T cells to regulatory T cells in blood pre-therapy and post-therapy

  Pre-dose through Cycle 3 Day 1

• Changes in the number of circulating immune related cells

  Pre-dose through Cycle 3 Day 1

• Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy

  Pre-dose through Cycle 3 Day 1

Study Arms (3)

ENT 1mg daily with pembro every 3 weeks

ACTIVE COMPARATOR

Entinostat daily in combination with pembrolizumab every three weeks

Drug: Entinostat; Drug: Pembrolizumab

ENT 5mg weekly with pembro every 3 weeks

ACTIVE COMPARATOR

Entinostat once weekly in combination with pembrolizumab every three weeks

Drug: Entinostat; Drug: Pembrolizumab

ENT 10mg bi-weekly with pembro every 3 weeks

ACTIVE COMPARATOR

Entinostat once every other week in combination with pembrolizumab every three weeks

Drug: Entinostat; Drug: Pembrolizumab

Interventions

Entinostat DRUG

HDAC (histone deacetylase) inhibitor

Also known as: SNDX-275, MS-275

ENT 10mg bi-weekly with pembro every 3 weeks; ENT 1mg daily with pembro every 3 weeks; ENT 5mg weekly with pembro every 3 weeks

Pembrolizumab DRUG

A selective humanized monoclonal antibody (mAb)

Also known as: Keytruda, MK-3475, SCH-900475

ENT 10mg bi-weekly with pembro every 3 weeks; ENT 1mg daily with pembro every 3 weeks; ENT 5mg weekly with pembro every 3 weeks

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completed Study SNDX-275-0140 (NCT02897778)
• Any AE or toxicity experienced in Study SNDX-275-0140 (NCT02897778) is resolved to less than or equal to Grade 1

You may not qualify if:

• Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The START Center for Cancer Care

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

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; Kidney Neoplasms

Interventions

entinostat; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Bronchial Diseases; Respiratory Tract Diseases; Digestive System Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Michael Meyers, MD, PhD

  Syndax Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 21, 2016
• Study Start: September 20, 2016
• Primary Completion: July 17, 2019
• Study Completion: February 9, 2021
• Last Updated: January 25, 2022

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)