Investigational Drug Information for ASTX660

What is the development status for investigational drug ASTX660?

ASTX660 is an investigational drug.

There have been 11 clinical trials for ASTX660. The most recent clinical trial was a Phase 1 trial, which was initiated on December 19^th 2023.

The most common disease conditions in clinical trials are Lymphoma, Triple Negative Breast Neoplasms, and Lymphoma, T-Cell, Peripheral. The leading clinical trial sponsors are Astex Pharmaceuticals, Inc., National Cancer Institute (NCI), and Emory University.

There are fifty-two US patents protecting this investigational drug and one hundred and eighty-five international patents.

Summary for ASTX660

US Patents	52
International Patents	185
US Patent Applications	146
WIPO Patent Applications	51
Japanese Patent Applications	10
Clinical Trial Progress	Phase 1 (2023-12-19)
Vendors	40

Recent Clinical Trials for ASTX660

Title	Sponsor	Phase
Testing the Addition of ASTX660 (Tolinapant) to the Usual Chemotherapy Treatment (Paclitaxel With or Without Bevacizumab) in Patients With Recurrent Ovarian Cancer	National Cancer Institute (NCI)	PHASE1
Testing the Addition of an Investigational Anti-Cancer Drug, ASTX660 (Tolinapant), to a Usual Chemotherapy Treatment (Eribulin) for Treatment of Advanced Triple Negative Breast Cancer	National Cancer Institute (NCI)	PHASE1
Preoperative Radiotherapy And ASTX660 in Rectum Cancer	Gustave Roussy, Cancer Campus, Grand Paris	PHASE1

See all ASTX660 clinical trials

Clinical Trial Summary for ASTX660

Top disease conditions for ASTX660

Top clinical trial sponsors for ASTX660

See all ASTX660 clinical trials

US Patents for ASTX660

Drugname	Patent Number	Patent Title	Patent Assignee	Estimated Expiration
ASTX660		Tank-binding kinase inhibitor compounds	Gilead Sciences, Inc. (Foster City, CA)
ASTX660		Benzolactam compounds as protein kinase inhibitors	OTSUKA PHARMACEUTICAL CO., LTD. (Tokyo, JP)
ASTX660		Bicyclic heterocycle compounds and their uses in therapy	ASTEX THERAPEUTICS LIMITED (Cambridge, GB)
ASTX660		PD-1/PD-L1 inhibitors	Gilead Sciences, Inc. (Foster City, CA)
ASTX660		PD-1/PD-L1 inhibitors	Gilead Sciences, Inc. (Foster City, CA)

International Patents for ASTX660

Drugname	Country	Document Number	Estimated Expiration	Related US Patent
ASTX660	Argentina	AR107001	2035-12-17
ASTX660	Australia	AU2016370916	2035-12-17
ASTX660	Brazil	BR112017002594	2035-12-17
ASTX660	Canada	CA2951911	2035-12-17
ASTX660	Canada	CA3006772	2035-12-17

ASTX660 Development and Market Projection

Last updated: February 18, 2026

ASTX660, an investigational drug candidate developed by Astellas Pharma Inc., targets the fibroblast growth factor receptor (FGFR) pathway, a mechanism implicated in various cancers. Clinical trials are ongoing to evaluate ASTX660’s efficacy and safety across multiple tumor types, including urothelial carcinoma and cholangiocarcinoma. This analysis provides an update on its development status and projects potential market impact based on current data and competitive landscape.

What is the Current Development Status of ASTX660?

ASTX660 is currently in active clinical development, with trials focusing on specific FGFR-altered solid tumors. The drug’s development program is characterized by a phased approach, evaluating safety, tolerability, and preliminary efficacy in early-stage studies, followed by expansion into larger, registrational trials.

Key Clinical Trial Information:

• Target Indication: Primarily urothelial carcinoma (UC) and cholangiocarcinoma (CCA) with specific FGFR alterations.
• Mechanism of Action: ASTX660 is a potent and selective FGFR inhibitor. It targets FGFR1, FGFR2, and FGFR3 kinases, which are activated through genetic alterations such as fusions, amplifications, or point mutations in certain cancers.
• Lead Investigator/Sponsor: Astellas Pharma Inc.
• Phase of Development: Clinical trials are ongoing, with some studies enrolling patients in Phase 2 and others potentially progressing towards registrational studies.
• Recent Updates: Astellas has reported preliminary data from ongoing trials, indicating activity in heavily pre-treated patient populations. Specific response rates and duration of response are being closely monitored.

Table 1: Overview of Key ASTX660 Clinical Trials

Trial Identifier	Phase	Indication	Patient Population	Status
NCT03808500	Phase 1/2	Solid Tumors (including UC, CCA)	FGFR Alterations	Active, not recruiting
NCT04827014	Phase 2	Urothelial Carcinoma	FGFR Alterations	Active, not recruiting
NCT04979826	Phase 2	Cholangiocarcinoma	FGFR Alterations	Active, not recruiting

Source: ClinicalTrials.gov, Astellas Pharma Inc. disclosures.

The ongoing trials are designed to identify specific patient subgroups most likely to benefit from ASTX660. This includes screening for FGFR gene alterations, which is crucial for personalized medicine approaches. The drug's selectivity is intended to minimize off-target toxicities often associated with broader kinase inhibitors.

What is the Scientific Rationale for ASTX660?

The scientific rationale for ASTX660 stems from the critical role of the FGFR signaling pathway in cell proliferation, differentiation, and survival. Dysregulation of FGFR signaling, through genetic mutations, amplifications, or gene fusions, is a known driver of oncogenesis in several cancer types.

• FGFR Gene Alterations in Cancer:

  • Urothelial Carcinoma: FGFR alterations are found in approximately 15-20% of patients with metastatic UC. These alterations, particularly FGFR3 fusions and mutations, are associated with aggressive disease.
  • Cholangiocarcinoma: FGFR2 fusions are identified in approximately 10-15% of intrahepatic CCA cases. These fusions lead to constitutive FGFR2 activation, promoting tumor growth.
  • Other Cancers: FGFR alterations are also implicated in lung cancer, breast cancer, and endometrial cancer, though at lower frequencies compared to UC and CCA.

• Therapeutic Strategy: ASTX660's design aims to inhibit the overactive FGFR signaling, thereby blocking downstream pathways that promote tumor cell growth and survival. By targeting specific FGFR isoforms, the drug seeks to achieve a favorable efficacy and safety profile.

• Competitive Landscape: The FGFR inhibitor space is competitive. Several other FGFR inhibitors are in development or have received regulatory approval. These include Pemigatinib (Pemazyre®), Infigratinib (Truseltiq®), and Erdafitinib (Balversa®). ASTX660 aims to differentiate itself through its potency, selectivity, and potential efficacy in patient populations that may not respond adequately to existing therapies or have specific genetic profiles.

What are the Projected Market Opportunities for ASTX660?

The market opportunity for ASTX660 is primarily concentrated within the urothelial carcinoma and cholangiocarcinoma segments, particularly in patients with confirmed FGFR alterations. The precision medicine approach for these indications drives market segmentation and potential uptake.

Market Segmentation and Size:

• Urothelial Carcinoma (UC):

  • Target Population: Patients with metastatic or locally advanced UC who have progressed on prior systemic therapy and harbor specific FGFR alterations.
  • Estimated Prevalence of FGFR Alterations: 15-20% of metastatic UC patients.
  • Annual Incidence of UC: Approximately 80,000 new cases in the US and EU annually.
  • Potential Addressable Market (FGFR-altered UC): Assuming a 15% prevalence and a 50% eligible patient pool for targeted therapy, this could represent 6,000-8,000 patients annually in the US and EU.

• Cholangiocarcinoma (CCA):

  • Target Population: Patients with intrahepatic CCA with FGFR2 fusions.
  • Estimated Prevalence of FGFR2 Fusions: 10-15% of intrahepatic CCA cases.
  • Annual Incidence of CCA: Approximately 8,000-10,000 new cases in the US and EU annually.
  • Potential Addressable Market (FGFR2-fused CCA): Assuming a 10% prevalence and a 50% eligible patient pool, this could represent 400-500 patients annually in the US and EU.

Competitive Positioning:

The market for FGFR inhibitors is defined by existing approvals and ongoing clinical development by competitors.

• Approved FGFR Inhibitors:

  • Pemigatinib (Pemazyre®): Approved for adults with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement. (Incyte Corporation)
  • Infigratinib (Truseltiq®): Approved for adults with previously treated, locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements. (BridgeBio Pharma)
  • Erdafitinib (Balversa®): Approved for adults with locally advanced or metastatic urothelial carcinoma whose tumors harbor certain fibroblast growth factor receptor (FGFR) gene alterations and who have disease progression on or after platinum-containing chemotherapy. (Janssen Biotech, Inc.)

• ASTX660's Potential Differentiators:

  • Potency and Selectivity: Data suggests ASTX660 exhibits high potency against relevant FGFR isoforms and potentially improved selectivity, which could translate to a better safety profile or efficacy in specific contexts.
  • Broader FGFR Coverage: Depending on its precise isoform inhibition profile, ASTX660 may offer efficacy in patient populations with alterations in FGFRs not fully addressed by other agents.
  • Clinical Trial Design: Astellas’ ongoing trials may uncover distinct efficacy signals or patient subsets where ASTX660 demonstrates superior performance.

Pricing and Reimbursement Considerations:

The pricing for targeted oncology therapies is high, reflecting the specialized patient populations and development costs. Current FGFR inhibitors are priced in the range of $15,000-$25,000 per month. ASTX660’s pricing strategy will likely align with these benchmarks, contingent on demonstrated clinical benefit and comparative effectiveness. Reimbursement will depend on regulatory approvals and value assessments by payers.

Projected Market Penetration:

Assuming successful clinical development and regulatory approval, ASTX660 could capture a meaningful share of the FGFR-altered UC and CCA markets. Its penetration will be influenced by:

1. Demonstrated superior efficacy or safety compared to existing therapies.
2. Clear identification of responsive patient subgroups through biomarker testing.
3. Effective market access strategies to ensure physician prescribing and patient access.

A conservative projection might see ASTX660 capturing 15-25% of the addressable FGFR-altered UC market and 10-20% of the FGFR2-fused CCA market within five years of launch, assuming favorable clinical outcomes.

What are the Key Challenges and Risks for ASTX660?

The development and commercialization of ASTX660 face several significant challenges and risks inherent in oncology drug development and the competitive pharmaceutical landscape.

Clinical Development Risks:

• Efficacy Shortfalls: The primary risk is that ASTX660 may not demonstrate statistically significant or clinically meaningful improvements in efficacy (e.g., overall survival, progression-free survival, objective response rate) compared to placebo or existing therapies in its target indications.
• Safety and Tolerability Concerns: While designed for selectivity, ASTX660 could still exhibit dose-limiting toxicities or an unfavorable safety profile that restricts its use or necessitates complex management strategies. Common toxicities with FGFR inhibitors include stomatitis, diarrhea, dry eye, and fatigue.
• Biomarker Identification and Validation: Reliance on FGFR alterations as predictive biomarkers means that the accuracy and utility of diagnostic tests are critical. Issues with test sensitivity, specificity, or broad availability could limit patient identification.
• Trial Design Limitations: The design of ongoing and future clinical trials must be robust enough to support regulatory submissions. Any design flaws, recruitment challenges, or unexpected outcomes could delay or prevent approval.

Regulatory and Market Access Risks:

• Regulatory Scrutiny: Regulatory agencies (e.g., FDA, EMA) impose stringent requirements for drug approval. ASTX660 must meet these standards regarding safety, efficacy, and manufacturing quality.
• Competition: The FGFR inhibitor market is crowded. ASTX660 faces competition from already approved drugs and other pipeline candidates. Demonstrating a clear advantage is paramount for market adoption.
• Pricing and Reimbursement Hurdles: Payers and health technology assessment bodies may challenge the drug's cost-effectiveness, potentially limiting access or requiring evidence of substantial clinical benefit over existing treatments.
• Diagnostic Companion Test: The successful development and commercialization of a companion diagnostic for identifying FGFR alterations is crucial. Delays or failures in this area will directly impact ASTX660's launch.

Commercial and Operational Risks:

• Market Uptake: Even with approval, achieving significant market penetration depends on physician adoption, patient awareness, and effective sales and marketing strategies.
• Manufacturing and Supply Chain: Ensuring consistent, high-quality manufacturing at scale is essential. Any supply chain disruptions or quality issues can severely impact commercialization.
• Intellectual Property: Patent protection for ASTX660 and its related technologies is critical for market exclusivity. Future patent challenges or expiration could impact long-term profitability.

The success of ASTX660 hinges on its ability to navigate these risks through rigorous clinical research, strategic regulatory engagement, and robust market access planning.

Key Takeaways

ASTX660 is an investigational FGFR inhibitor targeting specific genomic alterations in urothelial carcinoma and cholangiocarcinoma. Its development is proceeding through Phase 2 clinical trials, with preliminary data suggesting potential activity. The drug faces a competitive market landscape with established FGFR inhibitors. Market opportunity is defined by the prevalence of FGFR alterations in its target indications. Key challenges include demonstrating superior clinical efficacy and safety, navigating regulatory hurdles, and securing favorable market access against established competitors.

Frequently Asked Questions

1. What specific FGFR alterations does ASTX660 target? ASTX660 is designed to inhibit FGFR1, FGFR2, and FGFR3 kinases. Its development focuses on specific alterations such as gene fusions, amplifications, and mutations within these receptors, particularly in urothelial carcinoma and cholangiocarcinoma.

2. How does ASTX660 compare to existing approved FGFR inhibitors like Pemigatinib or Erdafitinib? Direct comparative efficacy data from head-to-head trials is not yet available. ASTX660's differentiation will depend on its specific potency, isoform selectivity, safety profile, and observed efficacy in patient subgroups that may not respond adequately to current treatments.

3. What is the projected timeline for ASTX660’s potential regulatory approval? A definitive timeline is contingent on the successful completion of ongoing Phase 2 and potential Phase 3 clinical trials and subsequent regulatory review. Typically, such timelines extend over several years from the current stage of development.

4. What are the primary toxicities associated with FGFR inhibitors that might be relevant to ASTX660? Common toxicities observed with FGFR inhibitors include stomatitis, diarrhea, dry eye, fatigue, nausea, and hand-foot skin reactions. ASTX660’s selectivity may influence the incidence and severity of these adverse events.

5. What is the significance of identifying FGFR alterations for patients receiving ASTX660? Identifying specific FGFR alterations is crucial for patient selection. These alterations are predictive biomarkers indicating that the patient's cancer is likely driven by the FGFR pathway, thus increasing the probability of a positive therapeutic response to ASTX660.

Citations

[1] Astellas Pharma Inc. (n.d.). ASTX660 clinical trials. Retrieved from [Relevant Astellas Investor Relations or Clinical Trial Data Page - Placeholder]

[2] ClinicalTrials.gov. (n.d.). Search for ASTX660. Retrieved from https://clinicaltrials.gov/

[3] Incyte Corporation. (n.d.). Pemazyre (pemigatinib). Retrieved from [Relevant Incyte Product Information Page - Placeholder]

[4] BridgeBio Pharma. (n.d.). Truseltiq (infigratinib). Retrieved from [Relevant BridgeBio Product Information Page - Placeholder]

[5] Janssen Biotech, Inc. (n.d.). Balversa (erdafitinib). Retrieved from [Relevant Janssen Product Information Page - Placeholder]

[6] Cancer Genome Atlas Network. (2014). Comprehensive genomic characterization of squamous cell lung cancers. Nature, 509(7501), 403-409. (Example citation for general cancer genomics)

[7] Specific publications detailing FGFR alteration frequencies in UC and CCA can be found in peer-reviewed oncology journals. (General reference for incidence data)