LCT + Brigatinib for Lung Cancer

Overseen By Yasir Elamin

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Brigatinib

Must not be taking: ALK-targeted TKIs

Disqualifiers: Other malignancy, CNS metastasis, cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

35 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, ongoing first-line brigatinib use is allowed if you meet certain criteria.

What data supports the effectiveness of the drug Brigatinib for lung cancer?

Research shows that Brigatinib is effective for patients with a specific type of lung cancer (ALK-positive non-small cell lung cancer) who have not responded well to another drug called crizotinib. It has been shown to work well in both early and later stages of treatment. ^{1 2 3 4 5}

Is brigatinib safe for use in humans?

Brigatinib is generally considered safe for use in humans, but it can cause lung-related side effects in some patients, such as lung toxicity, which is a rare but potentially serious condition. Early recognition and treatment of these side effects are important for the best outcomes. ^{6 7 8 9 10}

How is the drug Brigatinib unique for treating lung cancer?

Brigatinib is unique because it is an oral medication specifically designed for patients with a type of lung cancer that has a genetic change called ALK-positive, and it is particularly effective for those who have not responded to another drug called crizotinib. It also shows promise in treating brain metastases (cancer spread to the brain) in these patients. ^{1 2 9 11 12}

What is the purpose of this trial?

This early phase I trial studies the side effects and how well local consolidative therapy (LCT) and brigatinib works in treating patients with non-small cell lung cancer that is stage IV or has come back (recurrent). Giving LCT, such as surgery and/or radiation, after initial treatment may kill any remaining tumor cells. Brigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving LCT and brigatinib may work better in treating patients with non-small cell lung cancer.

Research Team

Yasir Y Elamin, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for adults with stage IV or recurrent non-small cell lung cancer (NSCLC) that have a specific ALK gene change. They must be healthy enough based on blood tests, not pregnant, and willing to use contraception. People can't join if they've had certain other treatments for NSCLC, uncontrolled health issues like heart disease or high blood pressure, active infections, or HIV.

Inclusion Criteria

Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Your heart's electrical activity is normal, as shown on a recent ECG test.

My lung cancer is at stage IV or has come back and cannot be treated with combined therapies.

Exclusion Criteria

I have had more than one treatment for my advanced cancer.

I have brain metastases needing more steroids recently.

I have lung conditions like interstitial disease or pneumonitis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Treatment with Brigatinib

Participants receive brigatinib orally once daily on days 1-28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.

8 weeks

Local Consolidative Therapy (LCT)

Participants undergo local consolidative therapy, such as surgery and/or radiation, for up to 3 weeks in the absence of disease progression or unacceptable toxicity.

3 weeks

Post-LCT Treatment with Brigatinib

Within 7 days after completion of LCT, participants receive brigatinib orally once daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Variable, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days and every 3 months for up to 2 years.

Up to 2 years

Treatment Details

Interventions

• Brigatinib
• Local Consolidation Therapy

Trial Overview The study is testing the combination of Local Consolidative Therapy (LCT), which includes surgery and/or radiation to remove remaining tumor cells after initial treatment, with a drug called Brigatinib that blocks enzymes tumors need to grow.

Participant Groups

Group I: Treatment (brigatinib, LCT) Experimental Treatment 2 Interventions

Patients receive brigatinib PO QD on days 1-28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo LCT for up to 3 weeks in the absence of disease progression or unacceptable toxicity. Within 7 days after completion of LCT, patients receive brigatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A population pharmacokinetic analysis of brigatinib, involving 442 participants (337 cancer patients and 105 healthy volunteers), revealed that its plasma concentrations are best described by a three-compartment model, indicating a complex absorption and distribution process.

The study found that factors like age, sex, and mild to moderate renal impairment do not significantly affect the drug's clearance, suggesting that no dose adjustments are necessary for these patient characteristics, which enhances the safety and ease of use of brigatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Brigatinib in Healthy Volunteers and Patients With Cancer. Gupta, N., Wang, X., Offman, E., et al.[2021]

In a phase 2 study of 222 patients with crizotinib-refractory ALK-positive NSCLC, brigatinib at 180 mg once daily showed a significantly higher median progression-free survival (PFS) of 16.7 months compared to 9.2 months for the 90 mg dose, indicating better efficacy at the higher dose.

Brigatinib demonstrated a high intracranial objective response rate of 67% in patients with brain lesions, along with a median duration of intracranial response of 16.6 months, suggesting it is effective for treating brain metastases in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. Huber, RM., Hansen, KH., Paz-Ares Rodríguez, L., et al.[2022]

Brigatinib demonstrated significant efficacy in treating ALK-positive advanced non-small cell lung cancer (NSCLC) in a heavily pretreated population, with a median progression-free survival (PFS) of 6.6 months and a disease control rate of 78.2% among 104 patients studied.

The median overall survival (OS) after starting brigatinib was 17.2 months, indicating that it can provide meaningful benefits even after multiple lines of prior treatment, including at least two ALK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib in patients with ALK-positive advanced non-small-cell lung cancer pretreated with sequential ALK inhibitors: A multicentric real-world study (BRIGALK study). Descourt, R., Perol, M., Rousseau-Bussac, G., et al.[2020]

Brigatinib is an effective treatment for patients with ALK-positive non-small cell lung cancer (NSCLC), showing a pooled objective response rate of 64% and a disease control rate of 88%, with particularly strong results in patients receiving it as a first-line treatment (mPFS of 24 months).

The treatment also demonstrates significant efficacy in patients with brain metastases, with an intracranial objective response rate of 54% and an intracranial progression-free survival of 19.26 months, while the most common adverse events, such as increased creatine phosphokinase and gastrointestinal issues, are manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of brigatinib in ALK-positive non-small cell lung cancer treatment: A systematic review and meta-analysis. Xing, P., Hao, X., Zhang, X., et al.[2022]

In clinical trials of brigatinib for advanced ALK+ non-small cell lung cancer (NSCLC), early-onset pulmonary adverse events (EOPEs) occurred in 8% of patients in phase 1/2, 6% in phase 2, and 3% in phase 3 studies, with a higher frequency linked to increased starting dosages.

A total of 3% of patients experienced severe (grade 3 or higher) EOPEs leading to treatment discontinuation, while 1.5% had milder events that allowed them to continue treatment, indicating that while EOPEs are a concern, many patients can manage them with appropriate interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early-Onset Pulmonary Events Associated With Brigatinib Use in Advanced NSCLC. Ng, TL., Narasimhan, N., Gupta, N., et al.[2022]

Brigatinib is an effective treatment for patients with metastatic ALK+ non-small-cell lung cancer (NSCLC) who have either progressed on or are intolerant to crizotinib, showing the ability to overcome crizotinib-resistant mutations and improve survival by about one year.

The drug is administered in a two-step dosage regimen, starting at 90 mg daily for the first week and then increasing to 180 mg daily, but it can cause side effects such as nausea, fatigue, and serious pulmonary-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib: Novel ALK Inhibitor for Non-Small-Cell Lung Cancer. Spencer, SA., Riley, AC., Matthew, A., et al.[2020]

Brigatinib, a second-generation ALK tyrosine kinase inhibitor, showed significant efficacy in patients with EML4-ALK-rearranged lung cancer who had developed resistance to previous treatments, achieving a 75.8% partial response rate and a median progression-free survival of 9.9 months across 35 patients.

The treatment was particularly effective in patients with brain metastases, with 54% showing a response, and brigatinib was well tolerated, indicating a favorable safety profile for patients transitioning from crizotinib or ceritinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of ALK-rearranged non-small-cell lung cancer with brigatinib as second or later lines: real-world observations from a single institution. Hochmair, M., Weinlinger, C., Schwab, S., et al.[2020]

In a study comparing brigatinib, ceritinib, and alectinib for treating crizotinib-refractory ALK+ non-small cell lung cancer, brigatinib showed significantly longer progression-free survival (PFS) and overall survival (OS) compared to ceritinib, with PFS medians of 15.7 months for ceritinib versus 18.3 months for brigatinib.

Brigatinib also demonstrated longer PFS compared to alectinib, with medians of 17.6 months for brigatinib versus 8.2 months for alectinib, although the OS results between these two were inconclusive.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer. Reckamp, K., Lin, HM., Huang, J., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Brigatinib in Healthy Volunteers and Patients With Cancer. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Brigatinib in Crizotinib-Refractory ALK+ NSCLC: 2-Year Follow-up on Systemic and Intracranial Outcomes in the Phase 2 ALTA Trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Long-Term Efficacy and Safety of Brigatinib in Crizotinib-Refractory ALK+ NSCLC: Final Results of the Phase 1/2 and Randomized Phase 2 (ALTA) Trials. [2023]

4. Ireland pubmed.ncbi.nlm.nih.gov

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]

5. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK-Inhibitor-Naive ALK+ Non-Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of brigatinib in ALK-positive non-small cell lung cancer treatment: A systematic review and meta-analysis. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Early-Onset Pulmonary Events Associated With Brigatinib Use in Advanced NSCLC. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Strengths and pitfalls of brigatinib in non-small cell lung cancer patients' management. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Brigatinib: Novel ALK Inhibitor for Non-Small-Cell Lung Cancer. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Lung Toxicity in Non-Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors: Report of a Peculiar Case and Systematic Review of the Literature. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Treatment of ALK-rearranged non-small-cell lung cancer with brigatinib as second or later lines: real-world observations from a single institution. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer. [2020]