Alectinib vs Chemotherapy for Non-Small Cell Lung Cancer

Recruiting at 220 trial locations

Overseen By Reference Study ID Number: BO40336 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: ALK inhibitors

Disqualifiers: Pregnancy, Prior radiotherapy, Liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months for alectinib, 4 cycles for chemotherapy

257 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized, active-controlled, multicenter, open-label, Phase III study is designed to investigate the efficacy and safety of alectinib compared with platinum-based in the adjuvant setting. Participants in the experimental arm will receive alectinib at 600 mg orally twice daily (BID) taken with food for 24 months. Participants in the control arm will receive one of the protocol specified platinum based chemotherapy regimens for 4 cycles. Following treatment completion, participants will be followed up for their disease until disease recurrence. At the time of disease recurrence, participants will enter a survival follow-up until death, withdrawal of consent or study closure, whichever occurs earlier.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking strong CYP450 3A inhibitors or inducers, you may need to stop them 14 days before starting alectinib and during the first three weeks of treatment.

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

The ALUR study showed that Alectinib significantly improved progression-free survival (the time during and after treatment that a patient lives with the disease without it getting worse) and had a better response rate in the brain compared to chemotherapy in patients with advanced ALK-positive non-small cell lung cancer who had already been treated with crizotinib. ^{1 2 3 4 5}

Is Alectinib safe for humans?

Alectinib is generally well tolerated but can cause serious side effects like skin toxicity and hyperbilirubinemia (high levels of bilirubin in the blood). It is considered safer than some other similar treatments, but patients should be monitored for adverse effects, especially if they have had prior treatments. ^{1 6 7 8 9}

How is the drug Alectinib different from chemotherapy for non-small cell lung cancer?

Alectinib is a targeted therapy specifically designed to block the action of a protein called ALK, which is involved in the growth of cancer cells, making it different from traditional chemotherapy that attacks rapidly dividing cells in general. This targeted approach can lead to fewer side effects and is particularly effective for patients with ALK-positive non-small cell lung cancer. ^{10 11 12 13 14}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with ALK-positive Non-Small Cell Lung Cancer who've had surgery to remove the tumor and are eligible for chemotherapy. They must have good blood and kidney function, agree to use effective contraception, and be able to follow study procedures. Excluded are those with significant health issues that could affect the study, prior cancer treatments or organ transplants, pregnant or breastfeeding women, certain GI disorders affecting drug absorption, HIV/AIDS patients, and those unlikely to comply with protocol.

Inclusion Criteria

My blood and kidney functions are within normal ranges.

I am willing and able to follow the study's schedule and procedures.

I am fully active or can carry out light work.

Exclusion Criteria

Known sensitivity to any component of study drug to which the patient may be randomized. This includes, but is not limited to, patients with galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption

Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry

I am not pregnant, breastfeeding, nor planning to become pregnant soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the experimental arm receive alectinib for 24 months, while the control arm receives platinum-based chemotherapy for 4 cycles

24 months for alectinib, 4 cycles for chemotherapy

Follow-up

Participants are monitored for disease recurrence and survival until death, withdrawal of consent, or study closure

Approximately 58 months

Survival Follow-up

Participants enter a survival follow-up phase until death, withdrawal of consent, or study closure

Up to approximately 8 years

Treatment Details

Interventions

• Alectinib

Trial Overview The trial compares alectinib—a targeted cancer drug taken orally twice daily for two years—with standard platinum-based chemotherapy given in four cycles. The goal is to see which treatment is more effective after lung cancer surgery in preventing disease recurrence. Participants will be randomly assigned to one of these treatments and followed up until disease recurrence or death.

Participant Groups

Group I: Alectinib Experimental Treatment 1 Intervention

Group II: Platinum-Based Chemotherapy Active Control 5 Interventions

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

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 significantly improved progression-free survival (PFS) compared to chemotherapy, with a median PFS of 10.9 months versus 1.4 months in patients with advanced ALK-positive non-small-cell lung cancer.

The objective response rate (ORR) was also much higher with alectinib at 50.6% compared to only 2.5% with chemotherapy, and it showed a remarkable CNS ORR of 66.7% in patients with measurable CNS metastases, indicating its efficacy in treating brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. Wolf, J., Helland, Å., Oh, IJ., et al.[2022]

Alectinib is a second-generation, orally active drug specifically designed to target ALK-positive non-small cell lung cancer (NSCLC) in patients who have developed resistance to the first-line treatment, crizotinib.

The FDA has granted Alectinib several designations, including orphan drug and breakthrough therapy status, highlighting its potential as a significant treatment option for patients with advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Medicine Tackles Clinical Resistance: Alectinib in ALK-Positive Non-Small Cell Lung Cancer Progressing on First-Generation ALK Inhibitor. Skoulidis, F., Papadimitrakopoulou, VA.[2019]

Alectinib, a second-generation ALK-tyrosine kinase inhibitor, is generally considered safer than other TKIs and is being tested for RET-rearranged non-small-cell lung cancer (NSCLC).

However, two patients experienced severe skin toxicity after receiving alectinib following treatment with an immune checkpoint inhibitor (ICI), highlighting the need for careful monitoring of adverse effects when combining these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Skin Toxicity Caused by Sequential Anti-PD-1 Antibody and Alectinib in Non-small-cell Lung Cancer: A Report of Two Cases and a Literature Review. Nishiyama, A., Hattori, Y., Takeuchi, S., et al.[2022]

Alectinib, while effective for treating advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements, can lead to serious side effects such as grade 4 hyperbilirubinemia, as seen in a patient after five months of treatment.

After discontinuing alectinib and using an artificial liver support system to manage the hyperbilirubinemia, the patient was successfully treated with ensartinib, achieving stable disease without recurrence of hyperbilirubinemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. Peng, L., Xiao, K., Cui, J., 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]

Cisplatin combined with either a vinca alkaloid or etoposide is highly effective in reducing mortality for patients with non-small cell lung cancer, as shown in meta-analyses comparing chemotherapy to supportive care.

Recent studies indicate that combining cisplatin-based chemotherapy with new agents and radiotherapy can significantly prolong survival and improve outcomes for patients with locally advanced non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. Shinkai, T., Saijo, N.[2018]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

Five new cytotoxic drugs have been introduced for treating non-small-cell lung cancer (NSCLC), showing comparable activity to cisplatin when used alone, and improved survival when combined with cisplatin.

Randomized studies indicate that these newer drugs not only enhance survival rates but also reduce side effects compared to older chemotherapy regimens, suggesting they are valuable options for patients, including those previously treated with platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for non-platinum chemotherapy in advanced NSCLC. Murren, JR.[2022]

Taxanes, such as paclitaxel and docetaxel, are effective chemotherapeutic agents for non-small cell lung cancer (NSCLC), showing significant anticancer activity in both single-agent and combination therapies, particularly with platinum compounds.

Docetaxel is not only effective as a first-line treatment for advanced NSCLC but is also FDA-approved as a second-line treatment for recurrent or relapsed cases, highlighting its importance in the management of this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes for advanced non-small cell lung cancer. Ramalingam, S., Belani, CP.[2019]

References

1. 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]

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

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer. [2022]

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

Chemotherapy versus alectinib for the treatment of crizotinib-pretreated ALK-positive patients with non small cell lung cancer: A protocol for systematic review and meta-analysis. [2023]

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

Personalized Medicine Tackles Clinical Resistance: Alectinib in ALK-Positive Non-Small Cell Lung Cancer Progressing on First-Generation ALK Inhibitor. [2019]

5. Greece pubmed.ncbi.nlm.nih.gov

Five-year Disease Control With Alectinib in a Patient With Metastatic ALK-rearranged Lung Adenocarcinoma. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

Severe Skin Toxicity Caused by Sequential Anti-PD-1 Antibody and Alectinib in Non-small-cell Lung Cancer: A Report of Two Cases and a Literature Review. [2022]

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

Successful Treatment with Ensartinib After Alectinib-induced Hyperbilirubinemia in ALK-Positive NSCLC. [2022]

8. 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]

9. England pubmed.ncbi.nlm.nih.gov

Successful alectinib desensitization in a patient with anaplastic lymphoma kinase-positive adenocarcinoma of the lung and alectinib-induced drug rash. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

[Chemotherapy for non-small cell lung cancer]. [2018]

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

Triplet combination chemotherapy and targeted therapy regimens. [2005]

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

Rationale for non-platinum chemotherapy in advanced NSCLC. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Taxanes for advanced non-small cell lung cancer. [2019]

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

New chemotherapeutic agents prolong survival and improve quality of life in non-small cell lung cancer: a review of the literature and future directions. [2022]