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Brigatinib

Brigatinib is an oral tyrosine kinase inhibitor being studied in clinical trials for the treatment of various ALK-positive cancers, particularly non-small cell lung cancer (NSCLC). This article summarizes key information from several clinical trials investigating the safety, efficacy, and optimal dosing of brigatinib in both adult and pediatric patients with ALK-positive cancers.

Table of Contents

What is Brigatinib?

Brigatinib is a medication used to treat certain types of lung cancer. It’s also known by the brand names Alunbrig™ and AP26113[1][2]. Brigatinib belongs to a class of drugs called tyrosine kinase inhibitors (TKIs), which work by blocking specific proteins that contribute to cancer growth[8].

What Conditions Does Brigatinib Treat?

Brigatinib is primarily used to treat a specific type of non-small cell lung cancer (NSCLC) that is ALK-positive. ALK stands for anaplastic lymphoma kinase, which is a protein that, when abnormally altered, can promote cancer growth. Brigatinib is used in patients with:

  • Advanced or metastatic ALK-positive NSCLC[2]
  • ALK-positive NSCLC that has progressed on or is intolerant to other ALK inhibitors like crizotinib, alectinib, or ceritinib[2][9]
  • Locally advanced or metastatic NSCLC[5]
Additionally, research is ongoing to evaluate brigatinib’s effectiveness in treating:
  • ALK-positive anaplastic large cell lymphoma (ALCL)[6]
  • Inflammatory myofibroblastic tumors (IMT)[6]
  • Other ALK-positive solid tumors[6]

How Does Brigatinib Work?

Brigatinib works by targeting and inhibiting the ALK protein. In some lung cancers, the ALK gene is abnormally rearranged, leading to the production of a fusion protein that drives cancer growth. Brigatinib blocks the activity of this abnormal ALK protein, which can slow down or stop the growth of cancer cells[2][8].

Dosage and Administration

Brigatinib is typically administered orally in tablet form. The common dosing regimen is:

  • 90 mg once daily for the first 7 days
  • If tolerated, the dose is increased to 180 mg once daily thereafter[2][5]
This dosing schedule is designed to help reduce the risk of early-onset side effects. Your doctor will determine the appropriate dose based on your individual needs and how well you tolerate the medication[5].

Efficacy of Brigatinib

Clinical trials have shown promising results for brigatinib in treating ALK-positive NSCLC:

  • Objective Response Rate (ORR): This measures how many patients have a significant reduction in tumor size. Studies have shown ORRs ranging from 50% to over 70% in various patient populations[2][9].
  • Progression-Free Survival (PFS): This is the length of time during and after treatment that a patient lives with the disease without it worsening. Brigatinib has demonstrated improved PFS compared to some other treatments[2].
  • Intracranial Response: Brigatinib has shown effectiveness in treating brain metastases, which are common in ALK-positive NSCLC[2][9].
It’s important to note that the effectiveness can vary depending on individual factors and prior treatments[9].

Side Effects and Safety

Like all medications, brigatinib can cause side effects. Some common side effects include:

  • Nausea and diarrhea
  • Fatigue
  • Headache
  • Cough
  • Muscle and joint pain
More serious side effects can include:
  • Interstitial Lung Disease (ILD): This is a group of lung conditions that cause scarring of lung tissue. It’s a rare but serious side effect that requires immediate medical attention[7].
  • High blood pressure
  • Slow heart rate
  • Vision problems
Your healthcare team will monitor you closely for these and other potential side effects[2][7].

Ongoing Research

Research on brigatinib is ongoing to further understand its effectiveness and expand its use:

  • Pediatric Studies: Clinical trials are evaluating the use of brigatinib in children and young adults with ALK-positive cancers, including ALCL and IMT[6][8].
  • First-line Treatment: Studies are investigating brigatinib as a first-line treatment for ALK-positive NSCLC[5].
  • Blood-based Testing: Research is exploring the use of blood tests to identify patients who might benefit from brigatinib, potentially reducing the need for invasive tissue biopsies[10].
  • Long-term Efficacy and Safety: Ongoing studies are monitoring the long-term effects and safety of brigatinib in various patient populations[7].
These ongoing studies aim to improve our understanding of brigatinib and potentially expand its use to help more patients[6][8][10].

Aspect Details
Drug Name Brigatinib (also known as AP26113, ALUNBRIG)
Drug Class Tyrosine Kinase Inhibitor (TKI)
Primary Target ALK (Anaplastic Lymphoma Kinase)
Main Indications ALK-positive Non-Small Cell Lung Cancer (NSCLC), ALK-positive Anaplastic Large Cell Lymphoma, ALK-positive Inflammatory Myofibroblastic Tumors
Common Dosing Regimen 90 mg once daily for 7 days, then 180 mg once daily
Key Efficacy Measures Objective Response Rate (ORR), Progression-Free Survival (PFS), Overall Survival (OS), Intracranial Response Rate
Safety Monitoring Adverse Events, Dose-Limiting Toxicities, Lung-related issues (e.g. pneumonitis), Liver function, Heart rhythm changes
Patient Populations Adults and children with ALK-positive cancers, including treatment-naive and previously treated patients
Ongoing Research Optimal dosing, efficacy in various ALK-positive cancers, use in pediatric patients, real-world effectiveness

FAQ

  • What is brigatinib and what types of cancer is it being studied for? Brigatinib is an oral tyrosine kinase inhibitor that targets the ALK (anaplastic lymphoma kinase) protein. It is being studied primarily for ALK-positive non-small cell lung cancer (NSCLC), as well as other ALK-positive cancers like anaplastic large cell lymphoma and inflammatory myofibroblastic tumors in both adults and children.
  • What are some of the main outcomes being measured in brigatinib clinical trials? Key outcomes being measured include objective response rate (percentage of patients whose tumors shrink), progression-free survival (time until cancer progresses), overall survival, safety/side effects, and quality of life. For patients with brain metastases, intracranial response is also being evaluated.
  • What is the typical dosing regimen for brigatinib in clinical trials? The most common dosing regimen studied is 90 mg once daily for 7 days, followed by an increase to 180 mg once daily. Some trials are also evaluating higher doses like 240 mg daily. Dosing may be adjusted based on tolerability.
  • Are there any clinical trials studying brigatinib in pediatric patients? Yes, there are ongoing clinical trials evaluating the safety, dosing, and efficacy of brigatinib in pediatric and young adult patients with ALK-positive cancers like anaplastic large cell lymphoma and inflammatory myofibroblastic tumors.
  • What are some of the potential side effects of brigatinib being monitored in clinical trials? Common side effects being monitored include gastrointestinal effects (nausea, diarrhea), fatigue, and lung-related issues like pneumonitis. Liver function, heart rhythm changes, vision problems, and muscle pain are also being assessed for safety.

Ongoing Clinical Trials on Brigatinib

  • Study of Brigatinib for Children and Young Adults with ALK+ Anaplastic Large Cell Lymphoma, Inflammatory Myofibroblastic Tumors, or Other Solid Tumors

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium Czechia Denmark Finland France +6

  • Study comparing brigatinib alone versus brigatinib with carboplatin and pemetrexed combination as first treatment for patients with advanced ALK-positive lung cancer

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France

  • Study on Brigatinib for Patients with ALK+ Non-Small Cell Lung Cancer

    Not recruiting

    1 1 1
    Investigated drugs:
    Spain

  • Study on Brigatinib and Durvalumab for Patients with Unresectable Stage III Non-Small Cell Lung Cancer with ALK Gene Change After Chemotherapy and Radiation Therapy

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Italy Poland Spain

  • Study on Brigatinib, Ceritinib, and Alectinib for Patients with Advanced ALK+ Non-Small Cell Lung Cancer

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

Glossary

  • ALK (Anaplastic Lymphoma Kinase): A protein that, when abnormally altered, can promote cancer growth. Brigatinib targets cancers with ALK gene changes.
  • Tyrosine Kinase Inhibitor (TKI): A type of targeted therapy that blocks specific enzymes called tyrosine kinases, which are involved in cancer cell growth and survival.
  • Non-Small Cell Lung Cancer (NSCLC): The most common type of lung cancer, accounting for about 80-85% of all cases.
  • Objective Response Rate (ORR): The percentage of patients whose cancer shrinks or disappears after treatment.
  • 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 either the date of diagnosis or the start of treatment that patients diagnosed with the disease are still alive.
  • Maximum Tolerated Dose (MTD): The highest dose of a drug that does not cause unacceptable side effects.
  • Recommended Phase 2 Dose (RP2D): The dose of a drug recommended for further testing in phase 2 clinical trials, based on safety and efficacy data from phase 1 trials.
  • Dose-Limiting Toxicity (DLT): Side effects that are severe enough to prevent an increase in drug dosage or require a decrease in dosage.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • RECIST (Response Evaluation Criteria in Solid Tumors): A standard way to measure how well a cancer patient responds to treatment, based on whether tumors shrink, stay the same, or get bigger.
  • Intracranial Response: The response of brain metastases (cancer that has spread to the brain) to treatment.
  • Quality of Life (QoL): A measure of a patient's overall well-being and ability to function in daily life during cancer treatment.

References

  1. https://clinicaltrials.gov/study/NCT01449461
  2. https://clinicaltrials.gov/study/NCT02094573
  3. https://clinicaltrials.gov/study/NCT06132867
  4. https://clinicaltrials.eu/trial/study-on-brigatinib-for-patients-with-alk-non-small-cell-lung-cancer/
  5. https://clinicaltrials.gov/study/NCT05721950
  6. https://clinicaltrials.gov/study/NCT04260009
  7. https://clinicaltrials.gov/study/NCT05100069
  8. https://clinicaltrials.eu/trial/study-of-brigatinib-for-children-and-young-adults-with-alk-anaplastic-large-cell-lymphoma-inflammatory-myofibroblastic-tumors-or-other-solid-tumors/
  9. https://clinicaltrials.gov/study/NCT03535740
  10. https://clinicaltrials.gov/study/NCT04074993