Alectinib + Crizotinib for Cancer

Not currently recruiting at 45 trial locations

Overseen By Reference Study ID Number: BO39694 www.roche.com/about_roche/roche_worldwide.htm

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: Alectinib, Crizotinib

Must not be taking: CYP3A inhibitors, inducers

Disqualifiers: Pregnancy, Breastfeeding, Serious adverse events, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two cancer drugs, alectinib (Alecensa) and crizotinib (Xalkori), to determine if they continue to benefit people with ALK- or RET-positive cancer. It provides ongoing treatment for those who benefited from these drugs in a previous study. Individuals with ALK- or RET-positive cancer who received successful treatment with alectinib or crizotinib in a prior Roche-sponsored study might be suitable for this trial. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to the potential availability of these treatments for more patients.

Will I have to stop taking my current medications?

The trial requires that you do not take strong cytochrome P450 (CYP) 3A inhibitors or inducers within 14 days before starting and during treatment with crizotinib. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

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

Research has shown that both alectinib and crizotinib have been tested for safety in patients with certain types of lung cancer. Alectinib can cause kidney problems in about 12% of patients, with severe cases in about 1.7%. However, it helps patients with advanced lung cancer live longer.

Crizotinib is generally considered safe but can cause vision problems in many patients. One study found that 92% of patients experienced some vision issues, mostly mild. It effectively treats specific types of lung cancer and has demonstrated good survival rates.

Overall, both treatments have been widely used, and their safety is well-documented. While they can cause side effects, many patients manage them well and benefit from their use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Alectinib and Crizotinib for cancer treatment because they target specific genetic mutations found in certain types of cancer, particularly non-small cell lung cancer (NSCLC) with ALK rearrangements. Unlike traditional chemotherapy that attacks rapidly dividing cells in general, Alectinib and Crizotinib are designed to block the ALK protein, hindering cancer cell growth with potentially fewer side effects. This targeted approach can lead to more effective treatments with improved quality of life for patients, offering hope for those who may not respond well to standard options like cisplatin or carboplatin-based therapies.

What is the effectiveness track record for alectinib and crizotinib in treating ALK- or RET positive cancer?

Research has shown that alectinib, one of the treatments in this trial, works effectively for patients with ALK-positive cancer. In studies, nearly 90% of patients did not experience cancer spreading to the brain at the first sign of disease progression. On average, cancer worsened after about 25.7 months with alectinib, compared to just 10.4 months with crizotinib. Crizotinib, another treatment option in this trial, has also demonstrated good results, doubling the time patients lived without cancer progression compared to chemotherapy. Patients reported better symptom relief and quality of life. Both alectinib and crizotinib are effective treatments for ALK-positive non-small-cell lung cancer, making them strong options for patients with this condition. ^{5 6 7 8 9}

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 patients with ALK- or RET-positive cancer who were part of a previous Roche-sponsored alectinib study and are still benefiting from alectinib or crizotinib. They must not be able to switch to commercial supply, agree to contraception if necessary, and cannot join if they're pregnant, breastfeeding, had no benefit in the parent trial, experienced severe side effects that led to discontinuation, or have unresolved serious adverse events.

Inclusion Criteria

I agree to use effective birth control or remain abstinent during and for 3 months after treatment.

I am benefiting from alectinib or crizotinib in a Roche trial but can't switch to commercial supply.

For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of study drug

Exclusion Criteria

I don't have any severe side effects from previous treatments that haven't improved.

I stopped taking alectinib or crizotinib before starting the new study drug.

I had to stop my cancer treatment for over 3 weeks because of side effects, but now I'm better or stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive continued treatment with alectinib or crizotinib as applicable, following the same dose and schedule as in the parent trial

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 continues treatment with either alectinib or crizotinib for participants previously enrolled in related trials. It aims to provide these drugs when commercial options aren't available and assess long-term benefits and safety for those still showing improvement.

How Is the Trial Designed?

Group I: Crizotinib Experimental Treatment 1 Intervention

Participants will receive crizotinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial.

Group II: Alectinib Experimental Treatment 1 Intervention

Participants will receive alectinib at the same dose and schedule and according to the same administration guidelines as they received at the time of discontinuation from the parent trial.

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 was found to have a favorable safety profile in a large-scale study of 1251 patients with ALK-positive non-small-cell lung cancer (NSCLC) in Japan, with 53.6% experiencing adverse drug reactions (ADRs), mostly mild to moderate in severity.

The study indicated that overall survival rates were significantly better in patients with good performance status, those who had not previously received crizotinib, and those receiving alectinib as a first-line treatment, suggesting its effectiveness in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of alectinib in a real-world surveillance study in patients with ALK-positive non-small-cell lung cancer in Japan. Masuda, N., Ohe, Y., Gemma, A., et al.[2021]

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 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 is a highly effective treatment for ALK fusion-gene positive advanced non-small cell lung cancer (NSCLC), with a 93.5% objective response rate in a phase 1-2 study involving ALK inhibitor-naive patients.

The drug is well tolerated, showing no grade 4 adverse events, and has a promising safety profile, with a 76% two-year progression-free survival rate and no progression of CNS lesions in patients with known metastases during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib: a review of its use in advanced ALK-rearranged non-small cell lung cancer. McKeage, K.[2022]

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 study of 34 untreated ALK-positive NSCLC patients with brain metastases, alectinib demonstrated significantly better progression-free survival (PFS) compared to crizotinib, with a median PFS of 32.8 months versus 8.0 months.

Alectinib also showed superior efficacy in treating brain lesions, with a median PFS that was not reached, while crizotinib had a median PFS of 8.5 months, indicating that alectinib may be a more effective treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib Together with Intracranial Therapies Improved Survival Outcomes in Untreated ALK-Positive Patients with Non-Small-Cell Lung Cancer and Symptomatic and Synchronic Brain Metastases: A Retrospective Study. Yin, Q., Li, P., Wang, P., et al.[2022]

In a study of 61 patients with ALK-rearranged non-small cell lung cancer (NSCLC), alectinib treatment resulted in significantly better overall survival (OS), time to treatment failure (TTF), and progression-free survival (PFS) compared to crizotinib.

Sequential treatment with crizotinib followed by alectinib after crizotinib failure showed a trend towards improved OS compared to alectinib alone, suggesting that combining therapies may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study. Ito, K., Hataji, O., Kobayashi, H., et al.[2022]

In a study of 211 patients with advanced ALK-positive NSCLC treated with alectinib, those with 40% or more ALK-positive cells experienced significantly better progression-free survival (PFS) and overall survival (OS) compared to those with fewer ALK-positive cells, indicating that the percentage of ALK-positive cells can predict treatment outcomes.

The overall response rate (ORR) was also higher in patients with a higher percentage of ALK-positive cells (87.2% vs. 68.5%), suggesting that alectinib is more effective in patients with a greater presence of ALK-positive tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The percentage of ALK-positive cells and the efficacy of first-line alectinib in advanced non-small cell lung cancer: is it a novel factor for stratification? (Turkish Oncology Group Study). Hizal, M., Bilgin, B., Paksoy, N., et al.[2023]

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]

Citations

1. alecensa.com alecensa.com/hcp/metastatic/efficacy/response-rate-cns-results.html

Results across endpoints Mobile infographic highlighting 84 % efficacy outcome achieved with ALECENSA® - mobile. Nearly 90% of patients had no CNS involvement at first progression ...

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

Real-world usage and clinical outcomes of alectinib among ... The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), ...

3. 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, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5455704/

Three-Year Follow-Up of an Alectinib Phase I/II Study in ALK ... The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for ...

5. 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.

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

ALECENSA® (alectinib) safety profile Renal impairment occurred in 12% of 533 patients treated with ALECENSA, including Grade ≥3 in 1.7% of patients, of which 0.4% were fatal events · The median time ...

7. onclive.com onclive.com/view/first-line-alectinib-yields-clinically-meaningful-os-benefit-in-advanced-alk-nsclc

First-Line Alectinib Yields Clinically Meaningful OS Benefit ... Alectinib improved overall survival in advanced ALK-positive NSCLC compared to crizotinib, though results were not statistically significant.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38598794/

Alectinib in Resected ALK-Positive Non-Small-Cell Lung ... Among patients with resected ALK-positive NSCLC of stage IB, II, or IIIA, adjuvant alectinib significantly improved disease-free survival as compared with ...

9. oncodaily.com oncodaily.com/oncolibrary/alex-trial

ALEX Trial Final Results at ESMO 2025: Alectinib ... Safety Profile · Median treatment duration was 28.1 months with alectinib versus 10.8 months with crizotinib, reflecting prolonged disease ...