Brigatinib + Chemotherapy for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Must be taking: Brigatinib
Must not be taking: Other TKIs
Disqualifiers: Other malignancies, CNS metastasis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
The goal of this clinical research study is to learn if the combination of brigatinib and either local consolidation therapy (such as radiotherapy or surgery) or chemotherapy (pemetrexed and carboplatin) can help to control the disease compared with brigatinib alone. The safety of these combinations will also be studied.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, you cannot receive other anti-cancer agents while participating in this study.
What data supports the effectiveness of the drug Brigatinib + Chemotherapy for Lung Cancer?
Brigatinib has been shown to be effective in treating patients with ALK-positive non-small cell lung cancer (NSCLC), especially those who have not responded to another drug called crizotinib. In studies, it improved the time patients lived without their cancer getting worse and worked well even in patients with cancer spread to the brain.12345
Is the combination of Brigatinib and chemotherapy safe for humans?
How is the drug brigatinib unique for treating lung cancer?
Brigatinib is unique because it is an oral medication specifically designed to target and inhibit the anaplastic lymphoma kinase (ALK) in non-small cell lung cancer, especially for patients who have developed resistance to other ALK inhibitors like crizotinib. It is effective in treating brain metastases and is well-tolerated, making it a valuable option for patients who have failed previous treatments.29101112
Eligibility Criteria
This trial is for individuals with advanced non-small cell lung cancer that tests positive for a change in the ALK gene. Participants should not have received brigatinib previously and must be fit enough for chemotherapy or local treatments like radiotherapy or surgery.Inclusion Criteria
I am 18 years old or older.
Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
My organ functions are within normal ranges.
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Exclusion Criteria
I have not had major surgery in the last 30 days.
I do not have any current infections requiring IV antibiotics.
I am not taking any other cancer treatments while in this study.
See 15 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive brigatinib alone or in combination with chemotherapy or local consolidation therapy
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Treatment Details
Interventions
- Brigatinib (ALK Inhibitor)
- Carboplatin (Chemotherapy)
- Pemetrexed (Chemotherapy)
Trial OverviewThe study is testing whether taking brigatinib along with either local consolidation therapy (like radiation or surgery) or chemotherapy drugs pemetrexed and carboplatin can better control lung cancer than just brigatinib alone.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Brigatinib MonotherapyExperimental Treatment1 Intervention
Given by mouth
Group II: Brigatinib + Local Consolidation Therapy (LCT)Experimental Treatment1 Intervention
Given by vein
Group III: Brigatinib + Carboplatin + PemetrexedExperimental Treatment3 Interventions
Given by vein
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
MD Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
References
Brigatinib: A Review in ALK-Inhibitor Naïve Advanced ALK-Positive NSCLC. [2021]Brigatinib (Alunbrig®) is an oral, potent and selective anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) tyrosine kinase inhibitor approved for treating adults with advanced ALK-positive non-small-cell lung cancer (NSCLC) not previously treated with an ALK inhibitor. In a multinational, phase III study (ALTA-1L) in this patient population, brigatinib significantly improved median blinded independent review committee-assessed progression-free survival (PFS), the confirmed objective response (OR) rate and the confirmed intracranial OR rate compared with crizotinib. Its tolerability profile in this study was manageable and no new safety concerns were identified. Although final analysis data are awaited with interest, brigatinib therapy extends the first-line treatment options available for standard of care in this patient population, including patients with CNS metastases.
Population Pharmacokinetics of Brigatinib in Healthy Volunteers and Patients With Cancer. [2021]Brigatinib is an oral tyrosine kinase inhibitor approved in multiple countries for the treatment of patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer who have progressed on or are intolerant to crizotinib. We report a population pharmacokinetic model-based analysis for brigatinib.
Randomized, open-label phase II study of brigatinib and carboplatin plus pemetrexed and brigatinib alone for chemotherapy-naive patients with ALK-rearranged non-squamous non-small cell lung cancer: treatment rationale and protocol design of the B-DASH study (WJOG 14720 L). [2023]The ALTA-1L study compared brigatinib with crizotinib in untreated ALK-rearranged non-small cell lung cancer (NSCLC) patients, demonstrating the efficacy of brigatinib. Although the median progression-free survival (PFS) of brigatinib group was 24.0 months, the one-year PFS rate was 70%. In the NEJ009 study, patients with EGFR mutations showed improved outcomes with gefitinib plus chemotherapy compared with gefitinib monotherapy. To evaluate the efficacy of the combination of brigatinib with chemotherapy for patients with ALK-rearranged NSCLC, we designed B-DASH study (WJOG 14720L).
Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer patients. [2019]Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease. Nowadays, brigatinib is under evaluation in different clinical trials exploring TKI-naive patients in the first-line setting. On the basis of its significant activity results, brigatinib received approval by the FDA for the treatment of patients with ALK-positive metastatic NSCLC who have progressed on or are intolerant to crizotinib.
Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. [2022]We report updated data from a phase 2 randomized study evaluating brigatinib in crizotinib-refractory anaplastic lymphoma kinase-positive NSCLC.
[Early Onset Pulmonary Events and Management Strategies during the Treatment of ALK Positive NSCLC Patients with Brigatinib]. [2023]Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase and its rearrangements occur in non-small cell lung cancer (NSCLC), resulting in signal dysregulation in kinase domain. As a new generation of potent ALK tyrosine kinase inhibitors (TKIs), Brigatinib was approved in China in March 2022 as a treatment for locally advanced or metastatic NSCLC patients with ALK rearrangement positive. Brigatinib significantly improved the survival, cranial efficacy and quality of life compared to Crizotinib in clinical trials. Brigatinib is generally well tolerated. Brigatinib has been one of the preferred treatments and an addition of options in ALK-rearranged NSCLC. Pulmonary toxicity is one of the adverse effects observed during the treatment of TKIs and deserves the intense attention of clinicians, despite of its low incidence rate. Pulmonary toxicity reported during the treatment of Brigatinib has shown distinct clinical presentations, such as early-onset (median time to onset, 2 days) and rapid tolerance and reversibility of symptoms. In view of this, the concept of early-onset pulmonary events (EOPEs) was proposed and established during the submission for regulatory review and approval. We focused on clinical characteristics, potential mechanism of etiology, and management strategies of EOPEs to provide clinicians evidence for better clinical decision support. .
Efficacy and safety of brigatinib in ALK-positive non-small cell lung cancer treatment: A systematic review and meta-analysis. [2022]Label="Background" NlmCategory="UNASSIGNED">Brigatinib is a central nervous system-active second-generation anaplastic lymphoma kinase (ALK) inhibitor that targets a broad range of ALK rearrangements in patients with non-small cell lung cancer (NSCLC). The current study aimed to analyze the pooled effects and adverse events of brigatinib in patients with ALK-positive NSCLC.
Early-Onset Pulmonary Events Associated With Brigatinib Use in Advanced NSCLC. [2022]We evaluated pulmonary adverse events observed within 7 days after drug initiation in phase 1 to phase 3 studies of the anaplastic lymphoma kinase (ALK) inhibitor brigatinib.
Brigatinib: Novel ALK Inhibitor for Non-Small-Cell Lung Cancer. [2020]We review here the pharmacology, pharmacokinetics, efficacy, safety, dosage and administration, potential drug-drug interactions and place in therapy of brigatinib for abnormal anaplastic lymphoma kinase (ALK) specific non-small-cell lung cancer (NSCLC).
Brigatinib in patients with ALK-positive advanced non-small-cell lung cancer pretreated with sequential ALK inhibitors: A multicentric real-world study (BRIGALK study). [2020]Brigatinib is a next-generation ALK inhibitor initially developed in ALK-positive NSCLC pretreated with crizotinib.
P-glycoprotein and breast cancer resistance protein restrict brigatinib brain accumulation and toxicity, and, alongside CYP3A, limit its oral availability. [2019]Brigatinib is an FDA-approved oral anaplastic lymphoma kinase (ALK) inhibitor for treatment of metastatic non-small cell lung cancer (NSCLC). Using genetically modified mouse models, we investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, and the multispecific drug-metabolizing enzyme CYP3 A in plasma pharmacokinetics and tissue distribution of brigatinib. In vitro, brigatinib was exceptionally well transported by human ABCB1 and mouse Abcg2, and efficiently by human ABCG2. Following oral brigatinib administration (10 mg/kg), brain accumulation was dramatically increased in Abcb1a/1b-/- (19.3-fold) and Abcb1a/1b;Abcg2-/-(41.8-fold), but not in single Abcg2-/- mice compared to wild-type mice. Brigatinib testis accumulation showed qualitatively similar behavior. mAbcb1a/1b and mAbcg2 together restricted systemic exposure of brigatinib: with both systems absent oral availability increased 1.9-fold. Coadministration of elacridar, an ABCB1/ABCG2 inhibitor, caused a pronounced increase (36-fold) in brain-to-plasma ratios of brigatinib, approaching the levels seen in Abcb1a/1b;Abcg2-/- mice. Unexpectedly, lethal toxicity of oral brigatinib was observed in mice with genetic knockout or pharmacological inhibition of mAbcb1a/1b and mAbcg2, indicating a pronounced protective role for these transporters. In Cyp3a-/- mice, brigatinib plasma exposure increased 1.3-fold, and was subsequently 1.8-fold reduced by transgenic overexpression of human CYP3 A4 in liver and intestine. The relative tissue distribution of brigatinib, however, remained unaltered. ABCB1 and ABCG2 thus limit brain accumulation, toxicity, and systemic exposure of brigatinib, whereas CYP3 A also markedly restricts its oral availability. Unexpected toxicities should therefore be carefully monitored when brigatinib is coadministered with ABCB1/ABCG2 inhibitors in patients. Collectively, these insights may support the clinical application of brigatinib.
Treatment of ALK-rearranged non-small-cell lung cancer with brigatinib as second or later lines: real-world observations from a single institution. [2020]The second-generation ALK tyrosine kinase inhibitor brigatinib has recently been approved in the European Union for use after crizotinib treatment in patients with EML4-ALK-rearranged lung cancer. In the current study, brigatinib was investigated as second-line or later-line treatment in 35 patients who had developed resistance to crizotinib, ceritinib, or alectinib. Most patients (68.6%) received brigatinib as second or third line (range: second to 12th line). In the total cohort, complete and partial responses were obtained for 9.1 and 75.8%, respectively. Overall median progression-free survival was 9.9 months, whereas the largest treatment cohort (brigatinib after crizotinib failure) showed a median progression-free survival of 8.4 months. Fifty-four percent of patients with baseline brain metastases responded to brigatinib treatment. Brigatinib was highly effective after crizotinib and ceritinib failure. Six patients had received alectinib as monotherapy, second-line, or third line before brigatinib; of these, four experienced partial responses and two progressed responses. Brigatinib treatment was well tolerated.