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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining local consolidative therapy (LCT) with the drug brigatinib for individuals with advanced non-small cell lung cancer (NSCLC). The researchers aim to determine if surgery or radiation (LCT) combined with brigatinib can more effectively target and kill cancer cells. The trial focuses on patients with stage IV or recurrent NSCLC, particularly those with an ALK gene rearrangement, who have not yet shown progression after initial treatment. This trial may suit those diagnosed with stage IV NSCLC and an ALK gene alteration. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that brigatinib is generally safe for treating certain types of lung cancer. Earlier studies found brigatinib to be a well-tolerated treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). Patients experienced significant benefits, particularly in preventing cancer from spreading to the brain, known as intracranial progression-free survival.

Importantly, various studies have tested brigatinib, demonstrating its effectiveness without causing severe side effects in most patients. The FDA has already approved it for treating ALK-positive NSCLC, indicating it has passed numerous safety checks for this condition.

For Local Consolidative Therapy (LCT), which includes treatments like radiation or surgery, research has shown it can improve patient outcomes, especially for those with advanced cancer. LCT has been found to extend both the time patients live without cancer returning and their overall survival.

Both treatments have a history of being manageable for patients, with brigatinib having more established safety data. Always consult a healthcare provider to understand how these treatments might fit personal health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about brigatinib for lung cancer because it offers a unique approach compared to standard treatments like chemotherapy and radiation. Unlike these traditional therapies, brigatinib specifically targets genetic mutations in cancer cells, which may lead to more effective results with potentially fewer side effects. Additionally, brigatinib is taken orally, making it a more convenient option for patients. This targeted therapy approach represents a promising advancement in the fight against lung cancer, providing hope for better outcomes and improved quality of life for patients.

What evidence suggests that LCT and brigatinib might be an effective treatment for non-small cell lung cancer?

Studies have shown that brigatinib effectively treats non-small cell lung cancer (NSCLC), particularly in patients with ALK-positive tumors. It has proven more effective than crizotinib, another cancer drug, in increasing progression-free survival, helping to prevent cancer from worsening. Research indicates that brigatinib also works well in the brain, which is crucial since cancer can spread there. Local consolidative therapy (LCT), such as surgery or radiation, extends survival by targeting remaining cancer cells after initial treatments. In this trial, participants will receive brigatinib followed by LCT, and then continue with brigatinib. Together, brigatinib and LCT might offer a powerful combination for fighting stage IV or recurrent NSCLC. ^{1 3 6 7 8}

Who Is on the Research Team?

Yasir Y Elamin, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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.

You are allergic or have a strong sensitivity to brigatinib or any of its ingredients.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12468605/

Real World Data on the Efficacy of Brigatinib in ALK-Positive ... Results of the ALTA 1L study showed superior outcomes for patients with ALK-positive NSCLC treated with brigatinib compared to patients treated with crizotinib.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8608

Alectinib vs. Brigatinib in ALK+ NSCLC Outcomes Among these, 1,009 patients received either alectinib (n=868) or brigatinib (n=141) as first-line therapy on HIRA data. Baseline characteristics ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225000455

Brigatinib Efficacy & Safety in ALK TKI-Naive ALK+ NSCLC Brigatinib demonstrated clinically meaningful systemic and intracranial efficacy in patients with ALK TKI-naive ALK+ NSCLC.

4. esmoopen.com esmoopen.com/article/S2059-7029(24)00385-5/fulltext

38P Treatment Patterns of Brigatinib for ALK+ NSCLC Brigatinib, an ALK tyrosine kinase inhibitor (TKI), showed superior clinical efficacy in 1L for ALK+ NSCLC compared to crizotinib in the phase III ALTA-1L trial ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9669367/

Efficacy and safety of brigatinib in ALK-positive non-small cell ... Brigatinib is effective in the treatment of patients with ALK-positive NSCLC, particularly showing robust intracranial PFS.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40011377/

Safety and Effectiveness of Brigatinib in Anaplastic ... Conclusions: Brigatinib was demonstrated to be a safe and effective treatment option for ALK-positive metastatic non-small cell lung cancer in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05200481

NCT05200481 | Study of Safety and Efficacy of Brigatinib ... The alternative hypothesis is that 86% or more of patients in Arm B would achieve progression free survival at 12 months. Official Title. A Phase II Randomized, ...

8. lungcancerjournal.info lungcancerjournal.info/article/S0169-5002(25)00685-3/abstract

Efficacy and safety of brigatinib after alectinib in patients with ... Median IRC-assessed progression-free survival (PFS) was 5.2 months (95 % CI: 3.7–7.3), and overall survival was 25.0 months (16.2–not reached).