Alectinib vs Crizotinib for Non-Small Cell Lung Cancer

(ALEX Trial)

Recruiting at 203 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: 4

Duration: Up to 33 months

303 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares two medications, alectinib and crizotinib, for treating a specific type of advanced lung cancer. The patients have not received any prior treatment for their cancer. Both drugs work by blocking a protein that helps the cancer cells grow. Alectinib has shown superior effectiveness and fewer side effects compared to crizotinib in treating this type of lung cancer.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot take certain drugs that affect liver enzymes or prolong the QT interval (a heart rhythm measure) within 14 days before starting the trial and during the study.

What data supports the effectiveness of the drug Alectinib for treating non-small cell lung cancer?

Research shows that Alectinib is more effective than Crizotinib for treating ALK-positive non-small cell lung cancer. It significantly increases the time patients live without the cancer getting worse and reduces the spread of cancer to the brain. ^{1 2 3 4 5}

Is Alectinib safe compared to Crizotinib for treating non-small cell lung cancer?

Research shows that Alectinib has a favorable safety profile compared to Crizotinib in treating non-small cell lung cancer, with studies indicating it is generally well-tolerated by patients. ^{4 5 6 7 8}

How does the drug Alectinib differ from Crizotinib for treating ALK-positive non-small cell lung cancer?

Alectinib is considered superior to Crizotinib for treating ALK-positive non-small cell lung cancer because it more than doubles the time patients live without the cancer getting worse and significantly reduces the risk of cancer spreading to the brain. It is also a preferred first-line treatment due to its effectiveness and manageable side effects. ^{1 3 4 9 10}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer that tests positive for ALK, who haven't had treatment before. They should be generally healthy, not pregnant or breastfeeding, and willing to use effective contraception. People can't join if they've taken certain drugs recently, have serious health issues affecting the study or drug absorption, a history of severe allergies to trial drugs' ingredients, or other cancers within 3 years.

Inclusion Criteria

My lung cancer is advanced or has returned, and tests show it's ALK-positive.

I am able to get out of my bed or chair and move around.

I have advanced lung cancer and haven't received any systemic treatment for it.

Exclusion Criteria

I have a stomach or liver condition.

My heart's electrical activity (QTc) is over 470 milliseconds, or I have slow heartbeat symptoms.

I haven't taken any medication that affects heart rhythm in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either alectinib or crizotinib until disease progression, unacceptable toxicity, withdrawal of consent, or death

Up to 33 months

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alectinib
• Crizotinib

Trial Overview The study compares two oral medications: Alectinib (600 mg twice daily) versus Crizotinib (250 mg twice daily), in people with untreated ALK-positive advanced NSCLC. Participants are randomly assigned to one of these treatments until their disease worsens or they experience unacceptable side effects.

Participant Groups

Group I: Alectinib Experimental Treatment 1 Intervention

Participants will receive alectinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Group II: Crizotinib Active Control 1 Intervention

Participants will receive crizotinib from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Alectinib is already approved in United States, European Union for the following indications:

Approved in United States as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Approved in European Union as Alecensa for:

• Metastatic ALK-positive non-small cell lung cancer (NSCLC)
• Adjuvant treatment following tumor resection in patients with ALK-positive NSCLC

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

Alectinib is a highly selective ALK inhibitor that has shown effectiveness against most crizotinib resistance mutations and has a favorable safety profile, making it a promising treatment for ALK-positive non-small-cell lung cancer (NSCLC).

The Phase III J-ALEX study demonstrated that alectinib significantly improves progression-free survival compared to crizotinib in treatment-naive ALK-positive NSCLC patients, suggesting it may become the preferred first-line therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib for treatment of ALK-positive non-small-cell lung cancer. Avrillon, V., Pérol, M.[2022]

Alectinib is an effective first-line treatment for adults with advanced ALK-positive non-small cell lung cancer (NSCLC), showing significantly improved progression-free survival compared to crizotinib and chemotherapy in clinical trials lasting up to 19 months.

The drug has a manageable safety profile, with most side effects being mild to moderate, making it a recommended option in treatment guidelines for patients with advanced ALK-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib: A Review in Advanced, ALK-Positive NSCLC. Paik, J., Dhillon, S.[2019]

Alectinib demonstrated superior efficacy compared to crizotinib in treating ALK-positive non-small cell lung cancer, with higher overall response rates and longer progression-free survival based on a meta-analysis of three studies involving 697 patients.

Alectinib was also associated with fewer adverse events than crizotinib, indicating it is not only more effective but also better tolerated, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis. Tang, H., Jin, L., Zhang, Z., et al.[2022]

Alectinib shows a high overall response rate of 70% and a disease control rate of 88% in treating non-small cell lung cancer, based on a meta-analysis of 8 studies involving 626 patients.

While alectinib is generally well-tolerated, it has a higher incidence of certain side effects like myalgia (18%) and anemia (25%) compared to the first-generation ALK inhibitor crizotinib, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis. Fan, J., Xia, Z., Zhang, X., et al.[2022]

In the phase III ALEX study involving patients with ALK+ non-small-cell lung cancer, alectinib showed superior efficacy compared to crizotinib, with patients reporting clinically meaningful improvements in lung cancer symptoms for a longer duration.

Alectinib also demonstrated better tolerability and health-related quality of life, with patients experiencing longer periods of symptom improvement and fewer treatment-related side effects compared to those on crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. Pérol, M., Pavlakis, N., Levchenko, E., et al.[2020]

In a phase III trial involving 107 patients with advanced ALK-positive non-small-cell lung cancer, alectinib demonstrated a significantly longer median progression-free survival (PFS) of 9.6 months compared to just 1.4 months for standard chemotherapy, indicating its superior efficacy.

Alectinib also showed a higher objective response rate in patients with central nervous system disease (54.2% vs. 0% for chemotherapy) and had a more favorable safety profile, with fewer grade ≥3 adverse events (27.1% for alectinib vs. 41.2% for chemotherapy).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Novello, S., Mazières, J., Oh, IJ., et al.[2022]

Alectinib demonstrated significantly better efficacy than crizotinib in treating ALK-positive non-small cell lung cancer, with improved progression-free survival (PFS) and overall survival (OS) based on a pooled analysis of 697 patients from three clinical trials.

In terms of safety, alectinib had a lower incidence of severe adverse effects compared to crizotinib, which was associated with higher rates of gastrointestinal issues and other side effects, making alectinib a more favorable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Zeng, Q., Zhang, X., He, S., et al.[2022]

References

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

Alectinib Superior to Crizotinib for ALK+ NSCLC. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Alectinib for treatment of ALK-positive non-small-cell lung cancer. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Alectinib: A Review in Advanced, ALK-Positive NSCLC. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis. [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes from the randomized phase III ALEX study of alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer. [2020]

7. Ireland pubmed.ncbi.nlm.nih.gov

Final progression-free survival results from the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Crizotinib versus Alectinib for the Treatment of ALK-Positive Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Alectinib as a treatment option following recovery from crizotinib-induced interstitial lung disease in patients with anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer. [2020]