Brigatinib + Chemotherapy for Lung Cancer

Overseen By Yasir Y Elamin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining brigatinib, a targeted cancer therapy, with treatments like chemotherapy or radiotherapy can better control lung cancer compared to brigatinib alone. Researchers seek to assess the effectiveness and safety of this combination. The trial targets individuals with stage IV non-small cell lung cancer (NSCLC) who have an ALK gene change. Candidates may qualify if they have used brigatinib or similar medications without disease progression. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that brigatinib is generally well-tolerated by patients with non-small cell lung cancer (NSCLC). It works effectively and has an acceptable safety profile. Common side effects include nausea, diarrhea, and fatigue, which can often be managed.

Studies on the combination of brigatinib with carboplatin and pemetrexed are ongoing. Early results suggest this combination is safe and effective. Some patients might experience stronger side effects from the chemotherapy drugs, such as hair loss and lower blood counts, but more specific safety information is still being gathered.

Combining brigatinib with local treatments like radiotherapy also appears safe. Real-world data suggest this combination could be effective, but more research is needed to confirm its long-term safety.

Overall, brigatinib alone and in combination with other treatments seems well-tolerated, though side effects can vary. Patients should discuss potential risks and benefits with their doctor before deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for lung cancer because Brigatinib offers a unique approach compared to standard options like chemotherapy alone. Brigatinib is a targeted therapy that inhibits a specific enzyme critical for cancer cell growth, which can potentially lead to more precise and effective treatment. The combination of Brigatinib with Carboplatin and Pemetrexed aims to enhance the effectiveness of chemotherapy by directly targeting cancer cells and supporting the body's defense against the disease. Additionally, the Brigatinib monotherapy provides a convenient oral option, making it easier for patients to adhere to their treatment regimens. Overall, these approaches could offer improved outcomes and fewer side effects than traditional chemotherapy treatments.

What evidence suggests that this trial's treatments could be effective for lung cancer?

Research shows that brigatinib effectively treats ALK-positive non-small cell lung cancer (NSCLC). Studies have found that patients taking brigatinib achieve better results than those taking crizotinib, with 67% not experiencing cancer progression after 12 months. In this trial, some participants will receive brigatinib alone, while others will receive brigatinib combined with chemotherapy drugs like carboplatin and pemetrexed. Early research suggests this combination is promising, especially for patients who haven't received prior treatment. Additionally, another group in this trial will receive brigatinib with local treatments like surgery or radiotherapy. This approach appears safe and potentially more effective, with one study showing patients went about 66 months without cancer progression. Overall, these findings suggest that brigatinib, either alone or with other treatments, could be a strong option for managing lung cancer. ^{3 6 7 8 9}

Who Is on the Research Team?

Yasir Y. Elamin

Principal Investigator

MD Anderson Cancer Cetner

Are You a Good Fit for This Trial?

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

My organ functions are within normal ranges.

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

I will use effective contraception or abstain from sex.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Brigatinib
• Carboplatin
• Pemetrexed

Trial Overview The 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.

How Is the Trial Designed?

Group I: Brigatinib Monotherapy Experimental Treatment 1 Intervention

Given by mouth

Group II: Brigatinib + Local Consolidation Therapy (LCT) Experimental Treatment 1 Intervention

Given by vein

Group III: Brigatinib + Carboplatin + Pemetrexed Experimental Treatment 3 Interventions

Given by vein

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

The B-DASH study is a phase II clinical trial designed to evaluate the efficacy of brigatinib combined with chemotherapy in patients with untreated ALK-rearranged non-small cell lung cancer (NSCLC), with a target sample size of 110 participants.

This study aims to determine if the combination therapy can improve progression-free survival (PFS) compared to brigatinib monotherapy, building on previous findings that showed brigatinib alone had a median PFS of 24 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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). Wakuda, K., Kenmotsu, H., Sato, Y., et al.[2023]

Brigatinib is a highly effective second-generation ALK tyrosine kinase inhibitor for treating non-small cell lung cancer (NSCLC) with ALK translocations, showing strong activity against various ALK resistance mutations.

It has demonstrated durable responses in patients who are resistant to crizotinib, including effectiveness in treating both lung and brain metastases, leading to its FDA approval for ALK-positive metastatic NSCLC patients who have progressed on or are intolerant to crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib for the treatment of ALK-positive advanced non-small cell lung cancer patients. Passaro, A., Prelaj, A., Pochesci, A., et al.[2019]

Brigatinib, an ALK tyrosine kinase inhibitor approved in China for treating advanced non-small cell lung cancer (NSCLC) with ALK rearrangements, has shown significant improvements in survival and quality of life compared to Crizotinib in clinical trials.

While Brigatinib is generally well tolerated, it can cause early-onset pulmonary toxicity, which occurs within a median of 2 days and is characterized by rapid tolerance and reversibility, highlighting the need for clinicians to monitor for these symptoms closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Early Onset Pulmonary Events and Management Strategies during the Treatment of ALK Positive NSCLC Patients with Brigatinib]. Yang, M., Luo, W., Zhou, Q.[2023]

In a multinational phase III study (ALTA-1L), brigatinib significantly improved progression-free survival and response rates compared to crizotinib in adults with advanced ALK-positive non-small-cell lung cancer, indicating its efficacy as a first-line treatment.

Brigatinib was found to have a manageable tolerability profile with no new safety concerns, making it a viable option for patients, including those with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brigatinib: A Review in ALK-Inhibitor Naïve Advanced ALK-Positive NSCLC. Hoy, SM.[2021]

Brigatinib, an ALK inhibitor for metastatic non-small cell lung cancer, shows significantly increased brain accumulation when the multidrug transporters ABCB1 and ABCG2 are genetically knocked out, indicating these transporters play a crucial role in limiting its central nervous system exposure and potential toxicity.

Coadministration of ABCB1/ABCG2 inhibitors can dramatically increase brigatinib's brain-to-plasma ratios, but this also raises concerns about unexpected toxicities, highlighting the need for careful monitoring in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

P-glycoprotein and breast cancer resistance protein restrict brigatinib brain accumulation and toxicity, and, alongside CYP3A, limit its oral availability. Li, W., Sparidans, RW., Wang, Y., et al.[2019]

Citations

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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

Real-world comparative outcomes of alectinib and ... Real-world comparative outcomes of alectinib and brigatinib in ALK-positive non–small cell lung cancer: A retrospective cohort analysis using ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02094573

A Study to Evaluate the Efficacy of Brigatinib (AP26113) in ... The purpose of this study is to evaluate the efficacy and safety of two different dosing regimens of brigatinib (AP26113) in participants with ALK-positive ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1810171

Brigatinib versus Crizotinib in ALK-Positive Non–Small- ... The rate of progression-free survival at 12 months was 67% in the brigatinib group (median not reached) and 43% in the crizotinib group (median, ...

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/27836716/

Activity and safety of brigatinib in ALK-rearranged non- ... Brigatinib shows promising clinical activity and has an acceptable safety profile in patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC.

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.8062

Safety and efficacy of brigatinib (AP26113) in advanced ... Activity and safety of brigatinib (BRG) in patients (pts) with ALK+ non–small cell lung cancer (NSCLC): Phase (ph) 1/2 trial results.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05200481

NCT05200481 | Study of Safety and Efficacy of Brigatinib ... This is a phase II randomized, open-labelled, non-comparative multicenter study in which ALK+ NSCLC patients who are naïve of treatment for advanced disease ...

9. alunbrig.com alunbrig.com/

ALUNBRIG® (brigatinib) for ALK+ Metastatic Non-Small ... ALUNBRIG is a prescription medicine used to treat adults with non-small cell lung cancer (NSCLC). It is not known if ALUNBRIG is safe and effective in children.