CLINICAL TRIALS PROFILE FOR GLASDEGIB MALEATE

All Clinical Trials for GLASDEGIB MALEATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT04655391 ↗	Glasdegib-Based Treatment Combinations for the Treatment of Patients With Relapsed Acute Myeloid Leukemia Who Have Undergone Hematopoietic Cell Transplantation	Not yet recruiting	National Cancer Institute (NCI)	Phase 1	2021-10-25	This phase Ib trial evaluates the best dose and effect of glasdegib in combination with venetoclax and decitabine, or gilteritinib, bosutinib, ivosidenib, or enasidenib in treating patients with acute myeloid leukemia that has come back (relapsed) after stem cell transplantation. Chemotherapy drugs, such as venetoclax and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Glasdegib, bosutinib, ivosidenib, and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Glasdegib inhibits the Sonic the Hedgehog gene. Venetoclax inhibits BCL-2 gene. Bosutinib is a tyrosine kinase inhibitor that inhibits BCR-ABL gene fusion. Ivosidenib inhibits isocitrate dehydrogenase-1 gene or IDH-1. Enasidenib inhibits isocitrate dehydrogenase-2 gene or IDH-2. This study involves an individualized approach that may allow doctors and researchers to more accurately predict which treatment plan works best for patients with relapsed acute myeloid leukemia.
NCT04655391 ↗	Glasdegib-Based Treatment Combinations for the Treatment of Patients With Relapsed Acute Myeloid Leukemia Who Have Undergone Hematopoietic Cell Transplantation	Not yet recruiting	City of Hope Medical Center	Phase 1	2021-10-25	This phase Ib trial evaluates the best dose and effect of glasdegib in combination with venetoclax and decitabine, or gilteritinib, bosutinib, ivosidenib, or enasidenib in treating patients with acute myeloid leukemia that has come back (relapsed) after stem cell transplantation. Chemotherapy drugs, such as venetoclax and decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Glasdegib, bosutinib, ivosidenib, and enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Glasdegib inhibits the Sonic the Hedgehog gene. Venetoclax inhibits BCL-2 gene. Bosutinib is a tyrosine kinase inhibitor that inhibits BCR-ABL gene fusion. Ivosidenib inhibits isocitrate dehydrogenase-1 gene or IDH-1. Enasidenib inhibits isocitrate dehydrogenase-2 gene or IDH-2. This study involves an individualized approach that may allow doctors and researchers to more accurately predict which treatment plan works best for patients with relapsed acute myeloid leukemia.
NCT03390296 ↗	OX40, Venetoclax, Avelumab, Glasdegib, Gemtuzumab Ozogamicin, and Azacitidine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia	Recruiting	National Cancer Institute (NCI)	Phase 1/Phase 2	2017-12-27	This phase Ib/II trial studies the side effects and best dose of anti-OX40 antibody PF-04518600 (OX40) and how well it works alone or in combination with venetoclax, avelumab, glasdegib, gemtuzumab ozogamicin, and azacitidine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as OX40, avelumab, and gemtuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Glasdegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as venetoclax and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving OX40, venetoclax, avelumab, glasdegib, gemtuzumab ozogamicin, and azacitidine may work better in treating patients with acute myeloid leukemia.
NCT03390296 ↗	OX40, Venetoclax, Avelumab, Glasdegib, Gemtuzumab Ozogamicin, and Azacitidine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia	Recruiting	M.D. Anderson Cancer Center	Phase 1/Phase 2	2017-12-27	This phase Ib/II trial studies the side effects and best dose of anti-OX40 antibody PF-04518600 (OX40) and how well it works alone or in combination with venetoclax, avelumab, glasdegib, gemtuzumab ozogamicin, and azacitidine in treating patients with acute myeloid leukemia that has come back or does not respond to treatment. Immunotherapy with monoclonal antibodies, such as OX40, avelumab, and gemtuzumab ozogamicin, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Glasdegib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as venetoclax and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving OX40, venetoclax, avelumab, glasdegib, gemtuzumab ozogamicin, and azacitidine may work better in treating patients with acute myeloid leukemia.

Clinical Trial Conditions for GLASDEGIB MALEATE

Condition Name

Condition Name for GLASDEGIB MALEATE
Intervention	Trials
Recurrent Acute Myeloid Leukemia	2
Refractory Acute Myeloid Leukemia	1

Condition MeSH

Condition MeSH for GLASDEGIB MALEATE
Intervention	Trials
Leukemia, Myeloid, Acute	2
Leukemia, Myeloid	2
Leukemia	2

Clinical Trial Locations for GLASDEGIB MALEATE

Trials by Country

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−

Trials by Country for GLASDEGIB MALEATE
Location	Trials
United States	2

Trials by US State

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−

Trials by US State for GLASDEGIB MALEATE
Location	Trials
California	1
Texas	1

Clinical Trial Progress for GLASDEGIB MALEATE

Clinical Trial Phase

Clinical Trial Phase for GLASDEGIB MALEATE
Clinical Trial Phase	Trials
Phase 1/Phase 2	1
Phase 1	1

Clinical Trial Status

Clinical Trial Status for GLASDEGIB MALEATE
Clinical Trial Phase	Trials
Not yet recruiting	1
Recruiting	1

Clinical Trial Sponsors for GLASDEGIB MALEATE

Sponsor Name

Sponsor Name for GLASDEGIB MALEATE
Sponsor	Trials
National Cancer Institute (NCI)	2
M.D. Anderson Cancer Center	1
City of Hope Medical Center	1

Sponsor Type

Sponsor Type for GLASDEGIB MALEATE
Sponsor	Trials
NIH	2
Other	2

Glasdegib Maleate: Clinical Trials Update, Market Analysis, and Projections

Introduction

Glasdegib maleate, marketed as DAURISMO®, is a significant advancement in the treatment of acute myeloid leukemia (AML), particularly for patients who are not candidates for intensive chemotherapy. Here, we will delve into the recent clinical trials, market analysis, and future projections for this drug.

Clinical Trials Update

Phase 3 BRIGHT AML 1019 Trial

The BRIGHT AML 1019 trial, a randomized, placebo-controlled phase 3 study, investigated the efficacy of glasdegib in combination with either intensive chemotherapy (cytarabine and daunorubicin) or non-intensive chemotherapy (azacitidine) in patients with untreated AML. The trial did not meet its primary efficacy endpoint, as the addition of glasdegib did not significantly improve overall survival in either the intensive or non-intensive treatment groups[1].

Safety and Adverse Events

The trial also reported that the proportion of patients experiencing treatment-emergent adverse events was similar between the glasdegib and placebo arms. Common adverse events included nausea, febrile neutropenia, and anemia in the intensive study, and anemia, constipation, and nausea in the non-intensive study[1].

Continuation Study

A continuation study of the non-intensive treatment group aimed to assess the long-term safety of glasdegib plus azacitidine. This open-label study found that participants taking glasdegib plus azacitidine had similar medical problems and side effects compared to those taking placebo plus azacitidine. The study highlighted the need for ongoing monitoring of patients receiving this combination therapy[3].

Mechanism of Action and Clinical Use

Targeting the Hedgehog Pathway

Glasdegib is a potent and selective inhibitor of the sonic hedgehog (Hh) signaling pathway, specifically targeting the smoothened (SMO) receptor. This pathway is often aberrantly activated in AML, making glasdegib a promising therapeutic agent[5].

Approved Indications

Glasdegib maleate is approved by the FDA and EMA for the treatment of newly diagnosed AML in patients aged 75 years and older, or in adults who cannot receive intensive induction chemotherapy, when used in combination with low-dose cytarabine[4][5].

Market Analysis

Current Market Position

Glasdegib maleate has carved a niche in the AML treatment landscape, particularly for older patients or those who are not suitable for intensive chemotherapy. Its approval has expanded treatment options for this patient population, offering a more favorable side effect profile compared to some other treatments like venetoclax with hypomethylation agents[5].

Competitive Landscape

The AML treatment market is highly competitive, with several drugs and combinations being studied and approved. However, glasdegib's unique mechanism of action and its use in combination with low-dose cytarabine make it a valuable addition to the treatment arsenal. The current gold standard for older AML patients involves venetoclax with hypomethylation agents, but glasdegib is being explored as a potential alternative due to its side effect profile[5].

Market Projections

Growth Potential

Despite the mixed results from the BRIGHT AML 1019 trial, glasdegib maleate is expected to see growth in its market share. This is driven by its approval for a specific patient population and ongoing research into new combinations and indications. The drug's favorable safety profile and the continuous need for effective AML treatments are key factors in its projected growth[5].

Future Research Directions

Ongoing and future clinical trials are focusing on exploring glasdegib in combination with other therapies to enhance its efficacy. For instance, new clinical combinations of glasdegib are being tested to potentially replace or complement existing treatments like venetoclax. These studies aim to optimize treatment outcomes and expand the drug's use in various cancer types beyond AML[5].

Side Effects and Safety Considerations

QTc Prolongation

One of the notable safety concerns with glasdegib is dose-dependent QTc prolongation, which requires careful monitoring in patients receiving this treatment[5].

Common Adverse Events

As observed in clinical trials, common adverse events associated with glasdegib include nausea, anemia, febrile neutropenia, and constipation. These side effects are generally manageable but necessitate close monitoring and appropriate management strategies[1][3].

Key Takeaways

• Clinical Trials: The BRIGHT AML 1019 trial did not meet its primary efficacy endpoint, but ongoing studies continue to explore glasdegib's potential in various combinations.
• Mechanism of Action: Glasdegib inhibits the sonic hedgehog signaling pathway by targeting the SMO receptor.
• Market Position: Glasdegib maleate is approved for treating newly diagnosed AML in specific patient populations and offers a favorable side effect profile.
• Growth Potential: The drug is expected to grow in market share due to its unique mechanism and ongoing research into new combinations.
• Safety Considerations: Monitoring for QTc prolongation and managing common adverse events are crucial.

FAQs

What is the primary mechanism of action of glasdegib maleate?

Glasdegib maleate acts by inhibiting the sonic hedgehog signaling pathway, specifically targeting the smoothened (SMO) receptor[5].

What are the approved indications for glasdegib maleate?

Glasdegib maleate is approved for the treatment of newly diagnosed AML in patients aged 75 years and older, or in adults who cannot receive intensive induction chemotherapy, when used in combination with low-dose cytarabine[4].

What were the findings of the BRIGHT AML 1019 trial?

The trial found that the addition of glasdegib to either intensive or non-intensive chemotherapy did not significantly improve overall survival in patients with untreated AML[1].

What are the common adverse events associated with glasdegib maleate?

Common adverse events include nausea, anemia, febrile neutropenia, and constipation[1][3].

Is glasdegib maleate associated with any specific safety concerns?

Yes, glasdegib maleate is associated with dose-dependent QTc prolongation, which requires careful monitoring[5].

Sources

1. ClinicalTrials.gov: Results from the randomized, phase 3 BRIGHT AML 1019 trial.
2. European Medicines Agency: Assessment report - Daurismo.
3. Pfizer: Clinical Study Results | Pfizer.
4. National Cancer Institute: Glasdegib Maleate.
5. DrugBank Online: Glasdegib: Uses, Interactions, Mechanism of Action.