Alectinib Pharmacogenomics for Lung Cancer

(Drugs-SNPs Trial)

Overseen By Han Xu, MD/PhD/FAPCR

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair

Must be taking: Alectinib

Must not be taking: Other anti-cancer therapies

Disqualifiers: Pneumonectomy, Pregnancy, Breast-feeding, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

600 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial investigates how genetic differences in patients with non-small cell lung cancer affect their response to ALECENSA treatment. By studying these genetic variations, researchers aim to improve the effectiveness and safety of the medication.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who cannot stop other anti-cancer therapies. It seems you may need to stop such treatments to participate.

What data supports the effectiveness of the drug Alectinib for lung cancer?

Alectinib has shown promising results in treating patients with ALK-positive non-small cell lung cancer (NSCLC), especially those who have developed resistance to the first-line drug crizotinib. In clinical trials, alectinib achieved a high response rate, with many patients experiencing rapid and sustained tumor shrinkage, and it was generally well tolerated. ^{1 2 3 4 5}

Is Alectinib safe for humans?

Alectinib has been studied for safety in patients with a specific type of lung cancer (ALK-positive non-small-cell lung cancer) and is generally considered safe, but some patients may stop treatment due to recurrence or side effects. It has received special designations from the FDA, indicating its potential benefits and safety profile. ^{1 3 4 6 7}

How is the drug Alectinib unique for treating lung cancer?

Alectinib is unique because it is a second-generation, orally active drug specifically designed to target and inhibit the anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC) patients who have developed resistance to the first-generation ALK inhibitor, crizotinib. It is highly effective in treating ALK-positive NSCLC, including cases with brain metastases, and has received special designations like orphan drug and breakthrough therapy due to its promising results. ^{1 2 3 4 5}

Research Team

Han Xu, MD/PhD/FAPCR

Principal Investigator

Medicine Invention Design, Inc. - IORG0007849

Han Xu, MD/PhD/FAPCR

Principal Investigator

Medicine Invention Design, Inc. - IORG0007849

Han Xu, MD/PhD/FAPCR

Principal Investigator

Medicine Invention Design, Inc. - IORG0007849

Eligibility Criteria

Adults over 22 with non-small cell lung cancer (NSCLC) who can undergo a lung tissue biopsy and have not used other anti-cancer therapies. They must be in good health otherwise, able to sign consent, and not pregnant or breastfeeding. Those with serious allergies, bleeding tendencies, multiple cancers, or severe illnesses cannot join.

Inclusion Criteria

My organs are working well.

I am physically active and can care for myself.

Sign an informed consent form

Exclusion Criteria

I have had a surgery to remove one of my lungs.

Treatment with other anti-cancer therapies and cannot be stopped currently

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Alectinib 600 mg orally twice daily and undergo genotyping for ALK and CYP4503A4 SNPs

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Alectinib

Trial Overview The study is looking at how genetic differences affect the way Alectinib works for NSCLC treatment. It involves precise gene sequencing to understand this relationship better and will compare usual Alectinib use against a study-specific approach.

Participant Groups

Group I: Alectinib - Usual Experimental Treatment 1 Intervention

* Usual ALECENSA - Alectinib * Chemotherapy (NDC...01) * Usual ALECENSA - alectinib hydrochloride capsule 600 mg orally twice daily * Usual Approach Group (NDC...01) * ALECENSA - alectinib hydrochloride capsule -- 600 mg orally twice daily

Group II: Alectinib - Study Experimental Treatment 1 Intervention

* Study ALECENSA - Alectinib * Chemotherapy (NDC...86) * Study ALECENSA - alectinib hydrochloride capsule 600 mg orally twice daily * Study Approach Group (NDC...86) * ALECENSA - alectinib hydrochloride capsule -- 600 mg orally twice daily

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?

Han Xu, M.D., Ph.D., FAPCR, Sponsor-Investigator, IRB Chair

Lead Sponsor

Trials

6

Recruited

2,400+

UnitedHealthcare

Collaborator

Trials

5

Recruited

594,000+

Findings from Research

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 is an effective next-generation ALK inhibitor for patients with metastatic ALK-positive non-small-cell lung cancer (NSCLC), showing improved progression-free survival and a reduction in brain metastases compared to crizotinib, especially in patients who are intolerant or have progressed on crizotinib.

Common side effects of alectinib include fatigue, constipation, and peripheral edema, with more serious effects being increases in liver enzymes and creatine phosphokinase, indicating it is generally well-tolerated in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib for advanced ALK-positive non-small-cell lung cancer. Ly, AC., Olin, JL., Smith, MB.[2019]

In a phase 2 study involving 87 patients with ALK-positive non-small-cell lung cancer who had progressed after crizotinib, alectinib demonstrated a 48% objective response rate, indicating significant clinical activity.

Alectinib was generally well tolerated, with most adverse events being mild (grade 1 or 2), although there were some serious events related to laboratory values; this suggests it could be a suitable treatment option for patients who have not responded to crizotinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Shaw, AT., Gandhi, L., Gadgeel, 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]

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 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]

References

1. 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]

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

Alectinib for advanced ALK-positive non-small-cell lung cancer. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. [2022]

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

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

6. 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]

7. 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]