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Last Updated: January 20, 2025

Investigational Drug Information for Entinostat


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What is the drug development status for Entinostat?

Entinostat is an investigational drug.

There have been 70 clinical trials for Entinostat. The most recent clinical trial was a Phase 2 trial, which was initiated on May 15th 2018.

The most common disease conditions in clinical trials are Breast Neoplasms, Carcinoma, and Lung Neoplasms. The leading clinical trial sponsors are National Cancer Institute (NCI), Syndax Pharmaceuticals, and Merck Sharp & Dohme Corp.

Recent Clinical Trials for Entinostat
TitleSponsorPhase
Phase I/II Evaluation of a Cancer Lysate Vaccine and Montanide(R) ISA-51 VG With Entinostat and Nivolumab as Adjuvant Therapy Following Chemoradiation Therapy With or Without Surgery for Locally Advanced Esophageal CancerNational Cancer Institute (NCI)Phase 1/Phase 2
Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors and LymphomasNational Cancer Institute (NCI)Phase 1/Phase 2
Phase I/II Trial of the Combination of Bintrafusp Alfa (M7824), Entinostat and NHS-IL12 (M9241) in Patients With Advanced CancerNational Cancer Institute (NCI)Phase 1/Phase 2

See all Entinostat clinical trials

Clinical Trial Summary for Entinostat

Top disease conditions for Entinostat
trials0246810121416182022Breast NeoplasmsCarcinomaLung Neoplasms[disabled in preview]
Top clinical trial sponsors for Entinostat
trials051015202530National Cancer Institute (NCI)Syndax PharmaceuticalsMerck Sharp & Dohme Corp.[disabled in preview]

See all Entinostat clinical trials

Development Update and Market Projection for the Drug Candidate: Entinostat

Introduction

Entinostat, a class I-specific histone deacetylase (HDAC) inhibitor, has been at the forefront of cancer research due to its promising results in various clinical trials. Developed by Syndax Pharmaceuticals, entinostat is being evaluated for its potential in treating multiple types of cancer, including breast cancer, non-small cell lung cancer, melanoma, and more.

Mechanism of Action

Entinostat works by inhibiting the activity of HDACs, which are enzymes that alter the structure of chromatin to control gene expression. This inhibition can lead to the suppression of immune suppressive cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), thereby enhancing the body’s immune response to tumors. This mechanism makes entinostat a potent candidate for combination therapies with immunotherapies like PD-1 and PD-L1 inhibitors[2][3][5].

Clinical Trials and Development Status

Advanced Breast Cancer

Entinostat has received Breakthrough Therapy designation from the FDA for the treatment of locally recurrent or metastatic estrogen receptor-positive (ER+) breast cancer. It is being evaluated in a Phase 3 clinical trial in combination with exemestane, an aromatase inhibitor, for postmenopausal women whose disease has progressed following non-steroidal aromatase inhibitor therapy. This trial, conducted by the ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute (NCI), has shown promising results in extending both progression-free survival and overall survival[4].

Combination Therapies

Entinostat is being tested in several combination therapies with major pharmaceutical companies. It is being evaluated in Phase 1b/2 clinical trials with Merck’s KEYTRUDA for non-small cell lung cancer and melanoma, and with Genentech’s TECENTRIQ for triple-negative breast cancer. These trials aim to assess the synergistic effects of entinostat when combined with immune checkpoint inhibitors, which could lead to improved response rates compared to monotherapy[3][5].

Other Cancer Indications

In addition to breast cancer, entinostat is being investigated for its efficacy in other cancer types, including ovarian cancer, head and neck cancer, bladder cancer, and renal cell cancer. These trials are part of Syndax’s broader strategy to establish proof of concept that entinostat can provide meaningful clinical benefits when combined with PD-1 or PD-L1 inhibitors[2].

Collaborations and Partnerships

Syndax has entered into non-exclusive collaborations with several major pharmaceutical companies, including Merck, Genentech, and Pfizer. These collaborations are aimed at accelerating the development and commercialization of entinostat across multiple tumor types. The MORPHEUS platform, a Phase Ib/II adaptive platform developed by Roche, is also being utilized to evaluate the combination of entinostat with other cancer immunotherapies[3][5].

Market Projection

Unmet Medical Needs

Entinostat addresses significant unmet medical needs, particularly in the treatment of advanced breast cancer and other cancers where patients have limited therapeutic options. The Breakthrough Therapy designation by the FDA underscores the potential of entinostat to offer substantial improvements over existing therapies[4].

Competitive Landscape

The market for cancer therapies, especially those involving immunotherapies and combination treatments, is highly competitive. However, entinostat’s unique mechanism of action and its ability to enhance the effectiveness of immune checkpoint inhibitors position it favorably. Syndax’s strategic collaborations with major pharmaceutical companies further strengthen its market potential[2][3].

Regulatory Pathway

Given the positive results from Phase 2 trials and the ongoing Phase 3 trials, Syndax is on track to pursue regulatory approval for entinostat in indications with significant unmet need and commercial potential. The FDA’s Breakthrough Therapy designation and the Special Protocol Assessment agreement with the NCI facilitate an expedited development and review process, which could lead to earlier market entry[4].

Future Directions

Chemoprevention

In addition to its therapeutic applications, entinostat is also being explored for chemoprevention, particularly in the context of Hereditary Diffuse Gastric Cancer (HDGC). Researchers at the University of Otago are testing entinostat in genetically complex organoid models and mouse models, with plans to validate the drug in CDH1 mutation carriers as part of a clinical trial[1].

Novel Drug Delivery Systems

Syndax and its collaborators are also investigating novel drug delivery systems that could enable the direct delivery of medications to the stomach tissue, potentially minimizing side effects and improving patient outcomes[1].

Key Takeaways

  • Mechanism of Action: Entinostat inhibits class I HDACs, reducing immune suppressive cells and enhancing the immune response to tumors.
  • Clinical Trials: Ongoing Phase 3 trials for advanced breast cancer and Phase 1b/2 trials for various other cancers in combination with immunotherapies.
  • Collaborations: Non-exclusive partnerships with Merck, Genentech, and Pfizer to accelerate development and commercialization.
  • Market Potential: Addresses significant unmet medical needs, particularly in advanced breast cancer, with a favorable competitive landscape.
  • Regulatory Pathway: Expedited development and review process due to Breakthrough Therapy designation and Special Protocol Assessment agreement.

FAQs

Q: What is the primary mechanism of action of entinostat?

A: Entinostat works by inhibiting class I histone deacetylases, which reduces the number and activity of immune suppressive cells like MDSCs and Tregs, thereby enhancing the immune response to tumors.

Q: For which cancer types is entinostat being evaluated?

A: Entinostat is being evaluated for advanced breast cancer, non-small cell lung cancer, melanoma, triple-negative breast cancer, ovarian cancer, head and neck cancer, bladder cancer, and renal cell cancer.

Q: What is the significance of the Breakthrough Therapy designation for entinostat?

A: The Breakthrough Therapy designation by the FDA allows for the expedited development and review of entinostat, indicating that it may demonstrate substantial improvement over existing therapies for serious or life-threatening diseases.

Q: Which companies is Syndax collaborating with for the development of entinostat?

A: Syndax is collaborating with Merck, Genentech, Pfizer, and Merck KGaA through non-exclusive clinical development agreements.

Q: What are the future directions for entinostat beyond its current therapeutic applications?

A: Entinostat is being explored for chemoprevention, particularly in Hereditary Diffuse Gastric Cancer, and novel drug delivery systems are being investigated to improve patient outcomes.

Sources

  1. No Stomach For Cancer: Development of drug for the treatment of Hereditary Diffuse Gastric Cancer (HDGC)[1].
  2. Syndax Pharmaceuticals, Inc.: Continue the development and commercialization of entinostat[2].
  3. Merck: Syndax and Merck Announce First Patients Dosed in Phase 1b/2 Clinical Trial of Entinostat and KEYTRUDA[3].
  4. Syndax Pharmaceuticals, Inc.: Syndax's Entinostat Receives Breakthrough Therapy Designation[4].
  5. Drug Development: Syndax Announces Clinical Collaboration With Genentech[5].

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