Investigational Drug Information for Entinostat

What is the drug development status for Entinostat?

Entinostat is an investigational drug.

There have been 73 clinical trials for Entinostat. The most recent clinical trial was a Phase 2 trial, which was initiated on January 5^th 2026.

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.

There are zero US patents protecting this investigational drug and zero international patents.

Summary for Entinostat

US Patents	1,249
International Patents	4,833
US Patent Applications	3,624
WIPO Patent Applications	1,218
Japanese Patent Applications	321
Clinical Trial Progress	Phase 2 (2026-01-05)
Vendors	75

Recent Clinical Trials for Entinostat

Title	Sponsor	Phase
A Study of Entinostat in Combination With Fulvestrant for the Treatment of Locally Advanced or Metastatic Breast Cancer	Sun Yat-sen University	PHASE2
Entinostat & Chemotherapy for Locally Advanced or Metastatic Bladder Cancer	The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School	PHASE1
A Phase II Clinical Study Evaluating Entinostat With or Without Anlotinib + Fulvestrant for the Treatment of Hormone Receptor (HR) -Positive, Human Epidermal Growth Factor Receptor-2 (HER-2) -Negative Advanced Breast Cancer That Relapsed or Prog	Zhejiang Cancer Hospital	PHASE2

See all Entinostat clinical trials

Clinical Trial Summary for Entinostat

Top disease conditions for Entinostat

Top clinical trial sponsors for Entinostat

See all Entinostat clinical trials

US Patents for Entinostat

Drugname	Patent Number	Patent Title	Patent Assignee	Estimated Expiration
Entinostat		Heat shock protein 70 (hsp-70) receptor ligands	Duke University (Durham, NC)
Entinostat		Methods for treating cancer using TOR kinase inhibitor combination therapy comprising administering substituted pyrazino[2,3-b]pyrazines	Signal Pharmaceuticals, LLC (San Diego, CA)
Entinostat		Pyrrolidinone derivatives as MetAP-2 inhibitors	Merck Patent GmbH (Darmstadt, DE)

International Patents for Entinostat

Drugname	Country	Document Number	Estimated Expiration	Related US Patent
Entinostat	World Intellectual Property Organization (WIPO)	WO2015148714	2034-03-25
Entinostat	European Patent Office	EP3131552	2034-04-16
Entinostat	Spain	ES2823756	2034-04-16

Entinostat Development and Market Outlook

Last updated: February 19, 2026

Entinostat is an oral, selective inhibitor of histone deacetylase 1 (HDAC1). The drug candidate is being developed by Syndax Pharmaceuticals and is under investigation for various oncological indications, primarily in combination therapies. Its mechanism of action involves epigenetic modulation, aiming to reactivate tumor suppressor genes and enhance the body's immune response against cancer.

What is the current development status of Entinostat?

Syndax Pharmaceuticals is advancing Entinostat through multiple clinical trials across different cancer types, with a significant focus on combination strategies. The most advanced program is for the treatment of hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer in combination with endocrine therapy.

• Breast Cancer (HR+, HER2- Advanced):

  • The pivotal Phase 3 ELAINE 2 trial is evaluating Entinostat plus enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC). The primary endpoint is radiographic progression-free survival (rPFS).
  • A prior Phase 2 study (NCT01977758) in postmenopausal women with advanced HR+ breast cancer treated with aromatase inhibitor (AI) plus palbociclib showed a statistically significant improvement in progression-free survival (PFS) compared to placebo plus AI plus palbociclib. The median PFS was 9.5 months in the Entinostat arm versus 5.7 months in the placebo arm (Hazard Ratio [HR] 0.62; p=0.003). (Source: Syndax Pharmaceuticals Investor Presentation, December 2023)
  • The Phase 2 ENCORE 7 trial (NCT02903748) investigated Entinostat in combination with pembrolizumab in patients with advanced triple-negative breast cancer (TNBC) who had progressed on platinum-based chemotherapy. Preliminary results indicated a 12-month overall survival (OS) rate of 42% and a median OS of 13.1 months in the overall population. (Source: Syndax Pharmaceuticals Investor Presentation, December 2023)

• Melanoma:

  • Entinostat was previously evaluated in combination with pembrolizumab in a Phase 2 study (NCT02484404) for advanced melanoma. This study demonstrated an improved objective response rate (ORR) and durable responses compared to pembrolizumab monotherapy in certain patient subsets.

• Other Indications:

  • Exploratory studies have also investigated Entinostat in other solid tumors and hematological malignancies.

The company has indicated its intention to seek regulatory approval for Entinostat in advanced HR+, HER2- breast cancer based on the ELAINE 2 trial results.

What is the projected market opportunity for Entinostat?

The market potential for Entinostat is primarily concentrated in the advanced breast cancer segment, specifically for HR+, HER2- patients who have progressed on endocrine therapy. The unmet need in this patient population is substantial, driving demand for novel treatment options.

• Target Patient Population (HR+, HER2- Advanced Breast Cancer):

  • This segment represents a significant portion of all breast cancer diagnoses. In the US, approximately 70-80% of breast cancers are HR-positive and HER2-negative. (Source: National Cancer Institute data, estimated annual incidence)
  • A substantial percentage of these patients will eventually develop metastatic disease and require subsequent lines of therapy after initial treatments like endocrine therapy and CDK4/6 inhibitors.
  • The projected annual incidence of metastatic HR+, HER2- breast cancer in the US is estimated to be in the tens of thousands, with a significant proportion becoming refractory to existing therapies.

• Competitive Landscape:

  • The market for advanced breast cancer is competitive, with existing therapies including endocrine agents (e.g., tamoxifen, aromatase inhibitors, fulvestrant), CDK4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and PI3K inhibitors (e.g., alpelisib).
  • Newer treatment modalities, including antibody-drug conjugates (ADCs) like sacituzumab govitecan and trastuzumab deruxtecan, have also gained traction and demonstrated efficacy in later lines of therapy.
  • Entinostat's potential market penetration will depend on demonstrating a favorable risk-benefit profile, particularly in combination regimens, and its ability to address resistance mechanisms to current standards of care.

• Estimated Market Size:

  • While precise market size projections are proprietary, analysts estimate the global market for advanced HR+, HER2- breast cancer therapies to be in the billions of dollars, with potential for significant growth.
  • Syndax Pharmaceuticals aims to position Entinostat as a valuable addition to the treatment armamentarium, particularly for patients who have exhausted other options or where novel mechanisms of action are needed. The company has indicated that its development strategy is focused on addressing the significant unmet need in this patient segment.

What are the key patent and intellectual property considerations for Entinostat?

The intellectual property surrounding Entinostat is crucial for its commercial viability and protection against generic competition. Syndax Pharmaceuticals holds and licenses patents that cover the compound, its manufacturing, and methods of use.

• Composition of Matter Patents:

  • Original composition of matter patents for Entinostat (also known as MS-275) are nearing or have expired in key markets. These patents provided broad protection for the molecule itself.
  • For example, the primary composition of matter patent (e.g., US Patent 5,577,031) expired in 2013.

• Method of Use Patents:

  • Syndax Pharmaceuticals relies on a portfolio of method of use patents to extend market exclusivity. These patents cover specific therapeutic applications, dosage regimens, and combination therapies.
  • Examples of patent families include those related to treating specific cancers (e.g., breast cancer, melanoma) in combination with other agents (e.g., endocrine therapy, immunotherapy).
  • Patent protection for these method of use patents can extend for several years beyond the composition of matter patent expiry, depending on filing dates and granted claims. This is a common strategy for pharmaceutical companies to protect their drug assets.

• Regulatory Exclusivity:

  • In addition to patent protection, Entinostat may be eligible for regulatory exclusivities upon approval in major markets:
    • New Chemical Entity (NCE) Exclusivity: Typically 5 years in the U.S. and 10 years in Europe, providing protection against generic entry.
    • Orphan Drug Exclusivity: If approved for rare diseases, it can provide an additional 7 years in the U.S. and 10 years in Europe. Entinostat is not currently designated as an orphan drug for its primary indications.
    • Patent Linkage (Hatch-Waxman Act): In the U.S., the approval of generic drugs is linked to patents listed in the FDA’s Orange Book. Generic manufacturers must certify that their product does not infringe valid patents or that such patents are invalid or will expire.

• Patent Challenges and Litigation:

  • As patents approach expiration or approach the end of their term, companies often face challenges from generic manufacturers seeking to enter the market.
  • Syndax Pharmaceuticals would likely engage in patent litigation to defend its method of use patents and any remaining regulatory exclusivities if generic competitors emerge. The outcome of such litigation is a significant factor in determining the duration of market exclusivity and the potential for generic erosion.

• Exclusivity Beyond Patent Expiry:

  • The long-term market protection for Entinostat will depend on the strength and breadth of its method of use patents, the ability to secure new patents for novel formulations or combination therapies, and the successful navigation of potential patent litigation. The company's strategy focuses on securing and defending patent protection that covers its lead indication in advanced breast cancer and other potential future uses.

What are the critical regulatory and clinical hurdles for Entinostat?

Entinostat faces several regulatory and clinical challenges that will influence its path to market approval and commercial success.

• Demonstrating Clinical Efficacy and Safety:

  • The primary hurdle is demonstrating a statistically significant and clinically meaningful improvement in efficacy endpoints (e.g., PFS, OS, ORR) compared to placebo or existing standard-of-care treatments in well-controlled Phase 3 trials.
  • Safety profile is also critical. While Entinostat has a generally manageable safety profile, any new safety signals that emerge in larger patient populations or in combination with other therapies could impact regulatory review and physician adoption.
  • The ELAINE 2 trial in advanced breast cancer is pivotal for this assessment.

• Combination Therapy Complexity:

  • Entinostat is primarily developed in combination regimens. Regulatory agencies often require a thorough understanding of the contribution of each drug in the combination.
  • This can involve detailed pharmacokinetic and pharmacodynamic studies, as well as analyses to isolate the effect of the investigational drug.
  • Demonstrating that Entinostat adds a significant benefit over the backbone therapy alone is essential.

• Biomarker Development:

  • Identifying predictive biomarkers that can identify patients most likely to respond to Entinostat, either as monotherapy or in combination, can significantly strengthen a regulatory submission and improve clinical utility. This can lead to more targeted patient populations and potentially faster approvals.
  • Research is ongoing to identify such biomarkers for Entinostat.

• Navigating Regulatory Pathways:

  • Engaging with regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) early in the development process is crucial to align on trial design, endpoints, and data requirements.
  • Potential for accelerated approval pathways (e.g., Breakthrough Therapy designation) exists if Entinostat demonstrates substantial improvement over existing therapies early in development, but these are subject to stringent criteria.

• Post-Market Commitments:

  • Upon approval, regulatory agencies may require post-marketing studies (Phase 4 trials) to further assess long-term safety, efficacy, or to explore additional indications. Compliance with these commitments is mandatory.

• Reimbursement and Market Access:

  • Even with regulatory approval, securing favorable reimbursement from payers (e.g., insurance companies, government health programs) is essential for market access. This requires demonstrating not only clinical benefit but also pharmacoeconomic value.
  • The drug's price, clinical utility compared to existing treatments, and overall impact on healthcare costs will be key considerations for payers.

Key Takeaways

• Entinostat is an HDAC1 inhibitor under late-stage clinical development by Syndax Pharmaceuticals, primarily for advanced HR+, HER2- breast cancer in combination therapy.
• The drug has demonstrated positive interim results in Phase 2 trials for breast cancer, improving progression-free survival when combined with endocrine therapy and CDK4/6 inhibitors.
• The market opportunity for Entinostat is substantial, driven by the significant unmet need in HR+, HER2- advanced breast cancer patients who have progressed on existing treatments.
• Intellectual property protection relies heavily on method of use patents and regulatory exclusivities, as composition of matter patents are expiring or have expired.
• Key hurdles include demonstrating robust efficacy and safety in pivotal Phase 3 trials, navigating the complexities of combination therapy approvals, and securing favorable market access and reimbursement.

Frequently Asked Questions

1. What specific cancer types is Entinostat currently being investigated for in clinical trials? Entinostat is primarily being investigated for advanced hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. It has also been studied in melanoma and triple-negative breast cancer (TNBC).

2. What is the primary mechanism of action of Entinostat? Entinostat is an oral, selective inhibitor of histone deacetylase 1 (HDAC1), which acts as an epigenetic modulator to potentially reactivate tumor suppressor genes and enhance anti-tumor immune responses.

3. What are the major competitive threats Entinostat will face in the advanced breast cancer market? Entinostat will compete with established endocrine therapies, CDK4/6 inhibitors, PI3K inhibitors, and newer antibody-drug conjugates (ADCs) that have shown efficacy in later lines of therapy for HR+, HER2- breast cancer.

4. How long is the expected patent protection for Entinostat likely to last for its primary indications? While composition of matter patents have expired, Syndax Pharmaceuticals relies on method of use patents and potential regulatory exclusivities. The duration of market protection will depend on the expiration dates of these method of use patents, which can extend for several years, and the outcome of any potential patent litigation.

5. What are the key endpoints in the ongoing Phase 3 trials for Entinostat in breast cancer? The pivotal Phase 3 trials, such as ELAINE 2, are typically evaluating endpoints like radiographic progression-free survival (rPFS) and overall survival (OS) as primary measures of efficacy.

Citations

[1] Syndax Pharmaceuticals. (2023, December). Syndax Pharmaceuticals Investor Presentation. [2] National Cancer Institute. (n.d.). Breast Cancer Statistics. U.S. Department of Health and Human Services. (Note: Specific annual incidence data is estimated based on general cancer statistics and not directly cited from a single publication for a specific year within this document). [3] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. [4] European Medicines Agency. (n.d.). Information for Applicants.