Clinical trial NCT02909452: Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-09-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 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
measure: Changes from baseline in laboratory results
timeFrame: Baseline through 90 day safety follow-up visit
measure: Changes from baseline in vital signs
timeFrame: Baseline through 90 day safety follow-up visit
measure: Changes from baseline in ECG results
timeFrame: Baseline through 90 day safety follow-up visit
Secondary outcomes:
measure: AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
measure: AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
measure: T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab
timeFrame: Pre-dose through Cycle 3 Day 1
Other outcomes:
measure: Ratio of effector T cells to regulatory T cells in blood pre-therapy and post-therapy
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Changes in the number of circulating immune related cells
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Changes in protein lysine acetylation in peripheral blood cells pre-therapy and post-therapy
timeFrame: Pre-dose through Cycle 3 Day 1
measure: Best overall tumor response
timeFrame: Baseline up to 2 years
Locations:
city: San Antonio
country: United States
facility: The START Center for Cancer Care
state: Texas
Study officials:
affiliation: Syndax Pharmaceuticals
name: Michael Meyers, MD, PhD
role: STUDY_DIRECTOR
References: