NeoplasmsPhase 1NCT02909452
Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors
A Phase 1 study testing Entinostat and Pembrolizumab in people with Neoplasms and Neoplasms, Glandular and Epithelial, run by Syndax Pharmaceuticals at 1 site in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type
- What is being tested?
- Entinostat and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Sep 2016to 9 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Continues to meet inclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
Who cannot join
- Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study
- Continues to meet exclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
Trial locations and contacts
1 site in 1 country.
United States1 site
The START Center for Cancer Care
San Antonio, Texas, 78229
About this study
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)
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
Read the 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.
- Conditions
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms
- Being tested
- Entinostat, Pembrolizumab
- Keywords
- entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor
- Medical subject headings
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms, Thoracic Neoplasms, Digestive System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntinostatDrug
Also called SNDX-275, MS-275
HDAC (histone deacetylase) inhibitor
PembrolizumabDrug
Also called Keytruda, MK-3475, SCH-900475
A selective humanized monoclonal antibody (mAb)
| Study group | Role | What they receive |
|---|---|---|
| ENT 1mg daily with pembro every 3 weeks | Active comparator | Entinostat daily in combination with pembrolizumab every three weeks Receives: Drug: Entinostat; Drug: Pembrolizumab |
| ENT 5mg weekly with pembro every 3 weeks | Active comparator | Entinostat once weekly in combination with pembrolizumab every three weeks Receives: 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 Receives: Drug: Entinostat; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline through 90 day safety follow-up visit
Changes from baseline in vital signs
Measured: Baseline through 90 day safety follow-up visit
Changes from baseline in ECG results
Measured: 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
Measured: Pre-dose through Cycle 3 Day 1
AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab
Measured: Pre-dose through Cycle 3 Day 1
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Measured: Pre-dose through Cycle 3 Day 1
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Measured: Pre-dose through Cycle 3 Day 1
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
Measured: Pre-dose through Cycle 3 Day 1
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab
Measured: Pre-dose through Cycle 3 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2016 (estimated)
- Study start20 Sep 2016
- Primary completion17 Jul 2019
- Study completion9 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Syndax Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Michael Meyers, MD, PhD, Study director, Syndax Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02909452
- Sponsor's protocol ID
- SNDX-275-0141
- Status last verified
- Jun 2018
- First submitted
- 13 Sep 2016
- Last updated
- 25 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: 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.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02909452
- Acronym / sponsor ID
- SNDX-275-0141
- Conditions
- Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type, Bronchial Neoplasms, Lung Neoplasms, Respiratory Tract Neoplasms
- Keywords
- entinostat, pembrolizumab, solid tumor, Histone Deacetylase Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Syndax PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 9 Feb 2021 (actual)
- First posted
- 21 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ENT 1mg daily with pembro every 3 weeks | Active comparator | Drug: Entinostat, Drug: PembrolizumabEntinostat daily in combination with pembrolizumab every three weeks |
| ENT 5mg weekly with pembro every 3 weeks | Active comparator | Drug: Entinostat, Drug: PembrolizumabEntinostat once weekly in combination with pembrolizumab every three weeks |
| ENT 10mg bi-weekly with pembro every 3 weeks | Active comparator | Drug: Entinostat, Drug: PembrolizumabEntinostat once every other week in combination with pembrolizumab every three weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
- Continues to meet inclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
Key exclusion criteria (2 listed)
- Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study
- Continues to meet exclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntinostatAlso: SNDX-275, MS-275HDAC (histone deacetylase) inhibitor | Drug | 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 |
| PembrolizumabAlso: Keytruda, MK-3475, SCH-900475A selective humanized monoclonal antibody (mAb) | Drug | 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 |
Primary outcome
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
Time frame: 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
Time frame: Baseline through 90 day safety follow-up visit
Changes from baseline in vital signs
Time frame: Baseline through 90 day safety follow-up visit
Changes from baseline in ECG results
Time frame: Baseline through 90 day safety follow-up visit
6 secondary outcomes
AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab
Time frame: Pre-dose through Cycle 3 Day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2022.
- Individual participant dataSharing planned: No. 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Meyers, MD, PhD study director
Syndax Pharmaceuticals
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Entinostat and Pembrolizumab in people with Neoplasms and Neoplasms, Glandular and Epithelial, run by Syndax Pharmaceuticals at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2022.