Breast Diseases, Bronchial Neoplasms, Carcinoma, Non-Small-Cell Lung, Digestive System Neoplasms, Endocrine Gland Neoplasms, Lung Diseases, Lung Neoplasms, Neoplasms, Neoplasms by Histologic Type, Neoplasms, Glandular and Epithelial, Renal Neoplasm, Respiratory Tract Neoplasms, Solid Tumors, Thoracic Neoplasms
Conditions
Keywords
entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor
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.
Interventions
DRUGEntinostat
HDAC (histone deacetylase) inhibitor
DRUGPembrolizumab
A selective humanized monoclonal antibody (mAb)
Sponsors
Merck Sharp & Dohme LLC
Syndax Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes from baseline in laboratory results | 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 |
| Changes from baseline in vital signs | Baseline through 90 day safety follow-up visit |
Secondary
| Measure | Time frame |
|---|---|
| T1/2 (elimination half life) 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 |
| Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab | Pre-dose through Cycle 3 Day 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 |
| 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 |
Other
| Measure | Time frame |
|---|---|
| Ratio of effector T cells to regulatory T cells in blood pre-therapy and post-therapy | Pre-dose through Cycle 3 Day 1 |
| Best overall tumor response | Baseline up to 2 years |
| Changes in protein lysine acetylation in peripheral blood cells 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 |
Countries
United States
Outcome results
None listed