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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ENT 1mg daily with pembro every 3 weeks | Active Comparator | Entinostat daily in combination with pembrolizumab every three weeks |
|
| ENT 5mg weekly with pembro every 3 weeks | Active Comparator | Entinostat once weekly in combination with pembrolizumab every three weeks |
|
| ENT 10mg bi-weekly with pembro every 3 weeks | Active Comparator | Entinostat once every other week in combination with pembrolizumab every three weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Entinostat | Drug | HDAC (histone deacetylase) inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | 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 | |
| Changes in the number of circulating immune related cells | Pre-dose through Cycle 3 Day 1 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Meyers, MD, PhD | Syndax Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The START Center for Cancer Care | San Antonio | Texas | 78229 | United States |
Data will be reviewed throughout the study by the sponsor, clinical research organization assisting with SAE management, and routine monitoring to safeguard the interests of the trial patients and to assess the safety of the interventions administered during the trial.
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|
| Pembrolizumab | Drug | A selective humanized monoclonal antibody (mAb) |
|
|
| 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 |
| Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab | 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 |
| Best overall tumor response | Baseline up to 2 years |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008171 | Lung Diseases |
| D001941 | Breast Diseases |
| D007680 | Kidney Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D004066 | Digestive System Diseases |
| D004700 | Endocrine System Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D014571 | Urologic Neoplasms |
| D014565 | Urogenital Neoplasms |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| C118739 | entinostat |
| C582435 | pembrolizumab |
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