Alunbrig (brigatinib) is a prescription medicine used to treat people with a specific form of non-small cell lung cancer (NSCLC). In anaplastic lymphoma kinase-positive (ALK+) metastatic NSCLC, a defect in the ALK genes causes part of the gene to break off and fuse with another gene, which produces an abnormal protein that can cause cells to grow and spread. Alunbrig is used with people whose cancer has spread to other parts of their body, and continues to progress after taking the ALK inhibitor Xalkori (crizotinib). Alunbrig also is used in patients unable to tolerate Xalkori.
This cancer treatment was developed by Ariad Pharmaceuticals, which was then acquired by Takeda. Alunbrig has received accelerated approval from the U.S. Food and Drug Administration (FDA) after previously receiving designations as a breakthrough therapy and as an orphan drug. A marketing authorization application (MAA) for the drug was submitted to the European Medicines Agency (EMA) in 2017.
How Alunbrig works
Alunbrig works by blocking the proteins made by the abnormal ALK gene. By binding to ALK, Alunbrig reduces its activity and was shown, in pre-clinical trials, to stop cell proliferation and have an anti-tumor effect. Unlike other ALK inhibitors, Alunbrig was able to inhibit 17 altered forms of the ALK protein, overcoming the resistance that tumor cells with mutated ALK present to other existing therapies that are not able to bind to as many variations.
Studies with Alunbrig
The FDA approval was based on the results of a Phase 2 clinical trial called ALTA (NCT02094573), which demonstrated a clinically meaningful and durable overall response rate in metastatic ALK-positive NSCLC patients. A total of 222 patients were recruited to receive Alunbrig by mouth at either 90 mg once daily, or 90 mg once daily for the first seven days and then at 180 mg once a day.
The overall response rate was 48 percent in the 90 mg group and 53 percent in the other group. The median duration of response to the treatment was 13.8 months in both groups. The most common adverse reactions to Alunbrig treatment were nausea, diarrhea, fatigue, cough, and headache (occurring in at least 25 percent of participants).
Ariad is currently recruiting up to 270 participants to participate in the ALTA-1L study (NCT02737501), a Phase 3 open-label trial to compare the efficacy of Alunbrig treatment to that of Xalkori in ALK-positive advanced NSCLC patients, who have not previously been treated with an ALK inhibitor.
During this trial, participants will be randomly administered either Alunbrig at a dose of 90 mg for seven days, and then 180 mg continuously, or Xalkori at a constant oral dose of 250 mg twice daily. The total estimated duration of the study is at least five years, including two years to recruit patients and at least three years for treatment and follow-up.
Another Phase 2 trial called the ARI-AT-002 trial (NCT02706626) is also currently recruiting 40 ALK-positive advanced NSCLC patients in the U.S. to assess the safety and effectiveness of Alunbrig in patients who have had first-line treatment for their cancer but still worsened. This includes patients whose disease progressed even after or while taking ALK inhibitors, or other anti-cancer drugs that act on tumors.
Note: Lung Cancer News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.