Ignite Creation Date:
2025-12-25 @ 4:07 AM
Ignite Modification Date:
2025-12-26 @ 3:03 AM
Study NCT ID:
NCT02453620
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-10-02
First Post:
2015-05-21
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Entinostat, Nivolumab, and Ipilimumab in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery or Locally Advanced or Metastatic HER2-Negative Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase 1 Study Evaluating Safety, Tolerability, and Preliminary Antitumor Activity of Entinostat and Nivolumab With or Without Ipilimumab in Advanced Solid Tumors
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial studies the side effects and best dose of entinostat and nivolumab when given together with ipilimumab in treating patients with solid tumors that have spread to other places in the body and usually cannot be cured or controlled with treatment (metastatic) or that cannot be removed by surgery (unresectable) or human epidermal growth factor receptor 2 (HER2)-negative breast cancer that has spread from where it started to nearby tissue or lymph nodes or other parts of the body. Entinostat is in a class of drugs called histone deacetylase (HDAC) inhibitors. It may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth (locally advanced/metastatic). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving entinostat and nivolumab together with ipilimumab may work better in treating in patients with solid tumors.
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of the combination of entinostat and nivolumab with or without ipilimumab in subjects with advanced solid tumors.
II. To determine the recommended phase II dose (RP2D) of the combination of entinostat and nivolumab with ipilimumab in subjects with advanced solid tumors and to further confirm the safety of the combination therapy in subjects with advanced HER2-negative breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate whether treatment with entinostat alone or in combination with nivolumab and ipilimumab results in an increase in the ratio of tumor antigen-specific effector T cells (Teff) to regulatory T cell (Treg) in tumor biopsies compared to baseline.
II. To describe preliminary anti-tumor activity of entinostat and nivolumab in combination with or without ipilimumab in patients with advanced solid tumors.
III. To assess preliminary anti-tumor activity in an expansion cohort of patients with advanced breast cancer treated at the RP2D.
EXPLORATORY OBJECTIVES:
I. To explore changes in immune-related biomarkers (e.g., expression of checkpoint receptors \[PD-1/PD-L1\], the number of myeloid derived suppressor cells \[MDSCs\], inflammatory T cell signature, T cell receptor \[TCR\] repertoire) in tumor biopsies or peripheral blood lymphocytes (PBL) pre- and post-therapy.
II. To correlate changes in immune-related biomarkers pre- and post-combination therapy with response.
III. To measure tumor-specific mutations and mutant neo-antigens recognized by patient T cells in tumor biopsies and to describe association with response.
IV. To evaluate changes in frequency of T cells recognizing tumor-specific mutant neo-antigens in peripheral blood lymphocytes (PBL) pre- and post-therapy.
V. To evaluate changes in candidate gene expression, including the azacitidine (AZA) immune genes (AIM genes) in malignant tissue, gene methylation silencing in circulating deoxyribonucleic acid (DNA) and malignant tissue pre- and post-therapy.
VI. To correlate the pharmacodynamic outcomes (e.g., safety, efficacy, and changes in gene methylation status) with the exposure of entinostat (i.e., pharmacokinetics) when co-administered with nivolumab with or without ipilimumab.
VII. To conduct pharmacogenomic association analyses to assess the potential clinical utility of CD86 gene polymorphisms as genetic determinants of immune mediated adverse events.
OUTLINE: This is a dose-escalation study.
Patients receive entinostat orally (PO) on days -14 and -7 and then weekly, nivolumab intravenously (IV) over 60 minutes on day 1 and then every 2 weeks, and ipilimumab IV over 90 minutes on day 1 and then every 6 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) as clinically indicated throughout the trial. Patients may undergo positron emission tomography (PET)/CT or bone scan throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.
After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.
I. To evaluate the safety and tolerability of the combination of entinostat and nivolumab with or without ipilimumab in subjects with advanced solid tumors.
II. To determine the recommended phase II dose (RP2D) of the combination of entinostat and nivolumab with ipilimumab in subjects with advanced solid tumors and to further confirm the safety of the combination therapy in subjects with advanced HER2-negative breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate whether treatment with entinostat alone or in combination with nivolumab and ipilimumab results in an increase in the ratio of tumor antigen-specific effector T cells (Teff) to regulatory T cell (Treg) in tumor biopsies compared to baseline.
II. To describe preliminary anti-tumor activity of entinostat and nivolumab in combination with or without ipilimumab in patients with advanced solid tumors.
III. To assess preliminary anti-tumor activity in an expansion cohort of patients with advanced breast cancer treated at the RP2D.
EXPLORATORY OBJECTIVES:
I. To explore changes in immune-related biomarkers (e.g., expression of checkpoint receptors \[PD-1/PD-L1\], the number of myeloid derived suppressor cells \[MDSCs\], inflammatory T cell signature, T cell receptor \[TCR\] repertoire) in tumor biopsies or peripheral blood lymphocytes (PBL) pre- and post-therapy.
II. To correlate changes in immune-related biomarkers pre- and post-combination therapy with response.
III. To measure tumor-specific mutations and mutant neo-antigens recognized by patient T cells in tumor biopsies and to describe association with response.
IV. To evaluate changes in frequency of T cells recognizing tumor-specific mutant neo-antigens in peripheral blood lymphocytes (PBL) pre- and post-therapy.
V. To evaluate changes in candidate gene expression, including the azacitidine (AZA) immune genes (AIM genes) in malignant tissue, gene methylation silencing in circulating deoxyribonucleic acid (DNA) and malignant tissue pre- and post-therapy.
VI. To correlate the pharmacodynamic outcomes (e.g., safety, efficacy, and changes in gene methylation status) with the exposure of entinostat (i.e., pharmacokinetics) when co-administered with nivolumab with or without ipilimumab.
VII. To conduct pharmacogenomic association analyses to assess the potential clinical utility of CD86 gene polymorphisms as genetic determinants of immune mediated adverse events.
OUTLINE: This is a dose-escalation study.
Patients receive entinostat orally (PO) on days -14 and -7 and then weekly, nivolumab intravenously (IV) over 60 minutes on day 1 and then every 2 weeks, and ipilimumab IV over 90 minutes on day 1 and then every 6 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) as clinically indicated throughout the trial. Patients may undergo positron emission tomography (PET)/CT or bone scan throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.
After completion of study treatment, patients are followed up every 3 months until disease progression and then every 6 months for up to 5 years.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2015-00741 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| SKCCC J15221 | None | None | View | |
| L9844 | None | None | View | |
| J15221 | None | None | View | |
| 9844 | OTHER | JHU Sidney Kimmel Comprehensive Cancer Center LAO | View | |
| 9844 | OTHER | CTEP | View | |
| UM1CA186689 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186690 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186691 | NIH | None | https://reporter.nih.gov/quic… | View |
| UM1CA186717 | NIH | None | https://reporter.nih.gov/quic… | View |