Alectinib vs Crizotinib for Non-Small Cell Lung Cancer

(ALEX Trial)

No longer recruiting at 231 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: Cytochrome P4503A drugs, QT prolonging drugs

Disqualifiers: Previous malignancy, GI disorder, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, alectinib (Alecensa) and crizotinib (Xalkori), to determine which is more effective for ALK-positive non-small cell lung cancer (NSCLC). Researchers aim to identify which treatment is safer and more effective for patients who have not yet received treatment for their advanced or metastatic lung cancer. Suitable candidates for this trial have been diagnosed with ALK-positive NSCLC and have not undergone prior treatment for their advanced cancer. Participants will receive one of the two medications and continue treatment until their cancer progresses or they experience significant side effects. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

A previous study found alectinib to be safe for people with ALK-positive non-small cell lung cancer. The most common side effects included fatigue, constipation, and swelling in the hands or feet. Importantly, no new or unexpected safety issues emerged.

Research has shown that crizotinib is generally well-tolerated. Common side effects include vision problems, diarrhea, and nausea. Like alectinib, the FDA has approved it for treating certain types of lung cancer, indicating a well-understood safety profile.

Both treatments have undergone testing in people, and previous research supports their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about Alectinib because it targets the ALK gene rearrangements in non-small cell lung cancer (NSCLC) more effectively than many existing treatments. Unlike Crizotinib, which was one of the first ALK inhibitors and is still commonly used, Alectinib has shown the ability to better penetrate the central nervous system, which is crucial for preventing and treating brain metastases. Additionally, Alectinib tends to have a more favorable side effect profile, making it a promising alternative for patients who may not tolerate other treatments well.

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

This trial will compare Alectinib and Crizotinib for treating ALK-positive non-small cell lung cancer (NSCLC). Research has shown that Alectinib is highly effective for this specific type of advanced lung cancer. In one study, patients taking Alectinib lived for an average of 25.7 months without their cancer worsening, compared to only 10.4 months for those taking Crizotinib. Additionally, 88.7% of patients on Alectinib were still alive after 24 months, and 73.3% were alive after 60 months. These results indicate that Alectinib provides longer-lasting control of the disease compared to Crizotinib. Participants in this trial will receive either Alectinib or Crizotinib to further evaluate these findings. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5744742/

Real-world usage and clinical outcomes of alectinib among ... Prognosis is poor for patients with metastatic disease, with the median survival <1 year because of delays in diagnosis.

2. alecensa.com alecensa.com/hcp/metastatic/efficacy/survival-results.html

Survival results for ALECENSA® (alectinib) PFS by IRC: In the ITT population, mPFS was 25.7 months for ALECENSA (95% CI: 19.9, NE) compared with 10.4 months with crizotinib (95% CI: 7.7, ...

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

Real-world comparative outcomes of alectinib and ... In this real-world study, both alectinib and brigatinib provided favorable survival outcomes in patients with ALK-positive NSCLC.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500225006543

Advanced-stage ALK-positive non–small-cell lung cancer ... Among 382 patients receiving 1L alectinib overall survival (OS) rate was 88.7 % and 73.3 % at 24 and 60 months, respectively. Median progression ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)04788-X/fulltext

final overall survival analysis of the phase III ALEX study Final mature OS results are from the updated data cut-off of 28 April 2025. Overall, 149 patients died: 76/152 (50.0%) in the alectinib arm and ...

6. alecensa.com alecensa.com/hcp/metastatic/side-effects-and-safety/safety-profile.html

ALECENSA® (alectinib) safety profile See safety data from the ALK+ mNSCLC pivotal clinical trial ... Alectinib versus crizotinib in untreated ALK-positive non–small-cell lung cancer.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31706099/

Pooled overall survival and safety data from the pivotal ... Alectinib demonstrated a median OS of 29.1 months (95% CI 21.3-39.0). No new or unexpected safety findings were observed. The most common all-grade AEs included ...

8. gene.com gene.com/assets/frontend/downloads/media/news-features/fda-approves-new-treatment-option-for-specific-type-of-lung-cancer/0327_Alecensa-Fact-Sheet_2019-09-04.pdf

ALECENSA® (alectinib) Fact Sheet NP28673 is a Phase II global, single-arm, open-label, multicenter trial evaluating the safety and efficacy of ALECENSA (600 mg orally twice daily) in 138 people ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6886236/

Pooled Systemic Efficacy and Safety Data from the Pivotal ... Alectinib demonstrated clinical efficacy and an acceptable safety profile in two phase II studies (NP28761 and NP28673). Here we report the pooled efficacy ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S1556086419302102

Updated Efficacy and Safety Data and Impact of the EML4 ... Alectinib continues to demonstrate superior investigator-assessed PFS versus crizotinib in untreated ALK-positive NSCLC, irrespective of EML4-ALK variant.