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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how the ALK gene affects the effectiveness of the drug Alectinib in treating non-small cell lung cancer (NSCLC) and how the CYP4503A4 gene influences the drug's side effects. Participants will take Alectinib, a medication already used for NSCLC, while researchers compare different treatment approaches. This trial suits those diagnosed with NSCLC, currently undergoing treatment, and willing to provide blood samples. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Research shows that Alectinib is generally well-tolerated by patients with non-small cell lung cancer. Studies have found no new or unexpected safety issues with this treatment. Common side effects include fatigue and constipation, but these are usually manageable. The FDA has already approved Alectinib for some lung cancer patients, indicating a strong safety record. Previous research supports its use, and patients have shown improved survival rates with this treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about Alectinib for lung cancer because it specifically targets and blocks ALK, a protein that fuels cancer growth in some patients. Unlike traditional chemotherapy that attacks all rapidly dividing cells, Alectinib focuses on cancer cells with this genetic abnormality, potentially leading to fewer side effects. Additionally, Alectinib is taken orally, making it more convenient compared to treatments that require hospital visits for administration. This precise targeting and ease of use make it a promising option for improving outcomes in lung cancer patients with ALK mutations.

What evidence suggests that Alectinib might be an effective treatment for non-small cell lung cancer?

Research shows that alectinib effectively treats ALK-positive non-small-cell lung cancer (NSCLC). In one study, 88.7% of patients taking alectinib survived after 2 years, and 73.3% survived after 5 years. Another study found that alectinib extended the time patients lived without their cancer worsening compared to crizotinib. Alectinib also reduced the risk of cancer recurrence or death by 76%. These strong results suggest that alectinib can effectively manage this type of lung cancer. Participants in this trial will receive either the standard or study approach of alectinib to further explore its pharmacogenomics. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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

Sign an informed consent form

My cancer can be measured by tests.

My organs are working well.

Exclusion Criteria

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

The prohibition of drug products

Pregnancy

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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. 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 ...

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. roche.com roche.com/media/releases/med-cor-2023-10-18

Roche's Alecensa reduces the risk of disease recurrence ... The study results showed that Alecensa® (alectinib) reduces the risk of disease recurrence or death by 76% (hazard ratio [HR]=0.24, 95% CI: 0.13-0.43, p<0.0001 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6005013/

Alectinib versus chemotherapy in crizotinib-pretreated ... In ALUR, alectinib significantly improved systemic and CNS efficacy versus chemotherapy in patients with crizotinib-pretreated anaplastic lymphoma kinase (ALK)- ...

6. 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 ...

7. onclive.com onclive.com/view/safety-data-help-affirm-adjuvant-alectinib-as-a-new-soc-in-alk-nsclc

Safety Data Help Affirm Adjuvant Alectinib as a New SOC ... Hidehito Horinouchi, MD, PhD, discusses safety data from the ALINA trial of adjuvant alectinib in ALK-positive non–small cell lung cancer.

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. roche.com roche.com/media/releases/med-cor-2024-04-19

FDA approves Roche's Alecensa as the first adjuvant ... Alecensa is now the first and only ALK inhibitor approved for people with ALK-positive early-stage NSCLC who have undergone surgery to remove their tumour.

10. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-alectinib-adjuvant-treatment-alk-positive-non-small-cell-lung-cancer

FDA approves alectinib as adjuvant treatment for ALK- ... FDA approves alectinib as adjuvant treatment for ALK-positive non-small cell lung cancer · Efficacy and Safety · Expedited Programs · Content ...