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(3S,3’S,3A’s,10A’s)-6-Chloro-3′-(3-Chloro-2-Fluorophenyl)-1′-(Cyclopropylmethyl)-6′-Methyl-2-Oxo-1,2,3′,3A’,10′,10A’-Hexahydro-1’H-Spiro[Indole-3,2′-Pyrrolo[2′,3′:4,5]Pyrrolo[1,2-B]Indazole]-7′-Carboxylic Acid

This article summarizes clinical trials investigating the use of BI 907828 (also known as brigimadlin) in treating various advanced solid tumors. BI 907828 is a novel drug that acts as an MDM2-p53 antagonist, potentially offering a new approach to cancer treatment. The trials focus on evaluating its safety, efficacy, and tolerability in patients with dedifferentiated liposarcoma, biliary tract cancer, pancreatic cancer, lung cancer, and other solid tumors.

Table of Contents

What is Brigimadlin?

Brigimadlin, also known as BI 907828, is a new drug being developed to treat various types of advanced solid tumors[1]. It is taken orally as a film-coated tablet and is currently being studied in several clinical trials to determine its safety and effectiveness[2].

How Does Brigimadlin Work?

Brigimadlin is a type of drug called an MDM2-p53 antagonist. This means it works by targeting a specific interaction in cancer cells[3]. To understand how it works, let’s break down some key terms:

  • MDM2: This is a protein that can suppress the activity of another important protein called p53.
  • p53: Often called the “guardian of the genome,” p53 helps prevent the growth of cancer cells and can trigger cell death in damaged cells.
  • Antagonist: This means the drug blocks or inhibits a specific action.

By blocking MDM2, brigimadlin allows p53 to become more active. This can help stop cancer cells from growing and potentially cause them to die off[3].

What Conditions Does Brigimadlin Treat?

Brigimadlin is being studied for the treatment of several types of advanced solid tumors, including:

  • Dedifferentiated liposarcoma (DDLPS): A rare type of cancer that develops in fatty tissue[1].
  • Biliary tract cancer: Cancer that occurs in the bile ducts[2].
  • Pancreatic ductal adenocarcinoma: A type of pancreatic cancer[2].
  • Non-small cell lung cancer (NSCLC)[2].
  • Triple negative breast cancer (TNBC)[2].
  • Colorectal cancer[2].
  • Urothelial bladder cancer[2].

These cancers are considered “advanced” when they have spread to other parts of the body or cannot be completely removed with surgery[1].

Clinical Trials

Brigimadlin is currently being studied in several clinical trials:

  • Brightline-4: A Phase III trial for patients with advanced dedifferentiated liposarcoma[1].
  • Brightline-2: A Phase IIa/IIb trial for patients with various advanced solid tumors[2].
  • EMPIRE: A study combining brigimadlin with another drug called ezabenlimab for patients with certain types of advanced solid tumors[3].
  • Brightline-1: A Phase II/III trial comparing brigimadlin to doxorubicin (a standard chemotherapy drug) in patients with advanced dedifferentiated liposarcoma[4].

Potential Benefits

While research is still ongoing, brigimadlin shows promise in several areas:

  • It may be effective against cancers that have stopped responding to other treatments[1].
  • It’s taken orally, which can be more convenient than intravenous treatments[1].
  • It targets a specific mechanism in cancer cells, which may lead to fewer side effects compared to traditional chemotherapy[3].
  • Early studies suggest it may be more effective than some current treatments for certain types of cancer[4].

Side Effects and Safety

As with all medications, brigimadlin can cause side effects. The full range of potential side effects is still being studied, but some that have been observed include:

  • Fatigue
  • Nausea
  • Changes in blood cell counts
  • Changes in liver function tests

It’s important to note that not everyone experiences side effects, and they can vary in severity. The clinical trials are closely monitoring all side effects to ensure patient safety[5].

Ongoing Research

Research on brigimadlin is ongoing, with several key areas of focus:

  • Determining the most effective dose[4].
  • Comparing its effectiveness to current standard treatments[4].
  • Studying its long-term safety[5].
  • Investigating its effectiveness when combined with other cancer treatments[3].

Conclusion

Brigimadlin (BI 907828) represents a promising new approach in the treatment of advanced solid tumors. While it’s still in the research phase, early results are encouraging. As with any new treatment, it’s important to remember that more study is needed to fully understand its benefits and risks. Patients interested in brigimadlin should discuss it with their healthcare provider to determine if participating in a clinical trial might be appropriate for their situation.

Trial Name Primary Objective Key Eligibility Criteria Primary Endpoint
Brightline-4 Evaluate safety and efficacy of brigimadlin in advanced dedifferentiated liposarcoma Histologically documented DDLPS, MDM2 amplification, TP53 wild-type Occurrence of treatment-emergent adverse events
Brightline-2 Assess efficacy, safety, and tolerability in MDM2 amplified, TP53 wild-type solid tumors Advanced solid tumors (biliary tract, pancreatic, lung, bladder), MDM2 amplification, TP53 wild-type Disease control rate
EMPIRE Investigate antitumor activity of ezabenlimab combined with BI 907828 Advanced solid tumors with tertiary lymphoid structures Disease control as per RECIST v1.1
Brightline-1 Compare brigimadlin to doxorubicin in first-line treatment of advanced DDLPS Advanced DDLPS, no prior systemic therapy Progression-free survival
Long-term Safety Study Evaluate long-term safety and tolerability of brigimadlin monotherapy Previous participation in a brigimadlin trial Occurrence of treatment-emergent adverse events

FAQ

  • What is BI 907828 and how does it work? BI 907828, also known as brigimadlin, is a novel drug that acts as an MDM2-p53 antagonist. It works by targeting the MDM2 protein, which normally inhibits the tumor suppressor p53. By blocking MDM2, BI 907828 allows p53 to become active and potentially halt tumor growth or induce cancer cell death.
  • What types of cancers are being studied with BI 907828? Clinical trials are investigating BI 907828 in various advanced solid tumors, including dedifferentiated liposarcoma, biliary tract cancer, pancreatic ductal adenocarcinoma, lung adenocarcinoma, and urothelial bladder cancer.
  • How is BI 907828 administered to patients? BI 907828 is administered orally as a film-coated tablet. The dosage and frequency may vary depending on the specific trial and patient factors.
  • What are the main objectives of these clinical trials? The main objectives of these trials are to evaluate the safety, efficacy, and tolerability of BI 907828. This includes assessing its ability to control disease progression, induce tumor responses, improve survival rates, and maintain quality of life for patients with advanced solid tumors.
  • Are there any specific genetic factors that make patients eligible for these trials? Yes, some trials require patients to have specific genetic characteristics. For example, patients with dedifferentiated liposarcoma must have MDM2 amplification and wild-type TP53 status. This is because the drug's mechanism of action is most effective in tumors with these genetic features.

Ongoing Clinical Trials on (3S,3’S,3A’s,10A’s)-6-Chloro-3′-(3-Chloro-2-Fluorophenyl)-1′-(Cyclopropylmethyl)-6′-Methyl-2-Oxo-1,2,3′,3A’,10′,10A’-Hexahydro-1’H-Spiro[Indole-3,2′-Pyrrolo[2′,3′:4,5]Pyrrolo[1,2-B]Indazole]-7′-Carboxylic Acid

  • Study on Long-Term Safety of BI 907828 for Patients with Solid Tumors Who Previously Participated in a Study with This Medicine

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Czechia Denmark France Germany Hungary +5

  • Study Comparing BI 907828 and Doxorubicin for Patients with Advanced Dedifferentiated Liposarcoma

    Not recruiting

    4 1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Czechia Finland France Germany Greece +6

  • Study on the Safety and Tolerance of BI 907828 in Patients with Advanced Dedifferentiated Liposarcoma

    Not recruiting

    3 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Italy

  • Study on the Effects of Ezabenlimab and BI 907828 in Adult Patients with Advanced or Metastatic Solid Tumors

    Not recruiting

    2 1 1
    Investigated drugs:
    France

  • Study on BI 907828 for Patients with Advanced Biliary Tract, Pancreatic, Lung, or Bladder Cancer

    Not recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium France Germany Spain

Glossary

  • MDM2-p53 antagonist: A type of drug that blocks the interaction between MDM2 (a protein) and p53 (a tumor suppressor), allowing p53 to become active and potentially stop cancer growth or cause cancer cell death.
  • Dedifferentiated liposarcoma (DDLPS): A type of soft tissue cancer that develops from fat cells and tends to be more aggressive than well-differentiated liposarcomas.
  • RECIST: Response Evaluation Criteria in Solid Tumors, a set of rules used to measure how well a cancer patient responds to treatment based on changes in tumor size.
  • Progression-free survival (PFS): The length of time during and after treatment that a patient lives with cancer without it worsening.
  • Overall survival (OS): The length of time from the start of treatment or diagnosis that patients are still alive.
  • Objective response (OR): A measurable response to treatment, typically referring to a reduction in tumor size.
  • ECOG performance status: A scale used to assess how a patient's disease affects their daily living abilities and determine appropriate treatment and prognosis.
  • Pharmacokinetics: The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • Pharmacodynamics: The study of how a drug affects the body, including its mechanism of action and relationship between drug concentration and effect.
  • Adverse event (AE): Any unfavorable and unintended sign, symptom, or disease temporarily associated with the use of a medical treatment or procedure.
  • TP53: A gene that provides instructions for making the p53 protein, which acts as a tumor suppressor by regulating cell division and preventing cells from growing and dividing too fast or in an uncontrolled way.
  • MDM2 amplification: An increase in the number of copies of the MDM2 gene, which can lead to overproduction of the MDM2 protein and suppression of p53 function.
  • Wild-type: The typical or normal form of a gene or organism, as it occurs in nature, without any mutations.
  • Tertiary lymphoid structures (TLS): Organized aggregates of immune cells that form in non-lymphoid tissues, often in response to chronic inflammation or cancer, and may play a role in the immune response against tumors.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-and-tolerance-of-bi-907828-in-patients-with-advanced-dedifferentiated-liposarcoma/
  2. http://clinicaltrials.eu/trial/study-on-bi-907828-for-patients-with-advanced-biliary-tract-pancreatic-lung-or-bladder-cancer/
  3. http://clinicaltrials.eu/trial/study-on-the-effects-of-ezabenlimab-and-bi-907828-in-adult-patients-with-advanced-or-metastatic-solid-tumors/
  4. http://clinicaltrials.eu/trial/study-comparing-bi-907828-and-doxorubicin-for-patients-with-advanced-dedifferentiated-liposarcoma/
  5. http://clinicaltrials.eu/trial/study-on-long-term-safety-of-bi-907828-for-patients-with-solid-tumors-who-previously-participated-in-a-study-with-this-medicine/