Ensartinib vs. Crizotinib for Non-Small Cell Lung Cancer

Recruiting at 128 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xcovery Holding Company, LLC

Must not be taking: Strong CYP3A inhibitors, Strong CYP3A inducers

Disqualifiers: Previous ALK TKI, CNS tumors, 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

Duration: 36 months

290 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of this study is to evaluate the efficacy and safety of X-396 (ensartinib) vs. crizotinib in patients with ALK-positive non-small cell lung cancer that have received up to 1 prior chemotherapy regimen and no prior ALK inhibitor.

Will I have to stop taking my current medications?

The trial requires stopping certain medications, such as strong CYP3A inhibitors, inducers, and substrates with a narrow therapeutic window, as well as anticancer herbal medications. If you are taking any of these, you will need to stop before joining the study.

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

Ensartinib has shown greater potency in inhibiting ALK activity and controlling brain metastases compared to crizotinib, especially in patients with ALK-positive non-small cell lung cancer. Clinical trials have demonstrated its promise as a more effective treatment option for these patients. ^{1 2 3 4 5}

What is known about the safety of Ensartinib and Crizotinib for human use?

Ensartinib and Crizotinib have been studied for safety in clinical trials. Ensartinib has shown safety in trials with both healthy volunteers and patients with non-small cell lung cancer. Crizotinib is generally safe but can cause side effects like vision problems, nausea, and more serious issues like liver damage and heart rhythm changes. ^{1 2 6 7 8}

How does the drug Ensartinib differ from other treatments for non-small cell lung cancer?

Ensartinib is a next-generation drug specifically designed to target ALK-positive non-small cell lung cancer, offering greater potency in inhibiting ALK activity and better control of brain metastases compared to crizotinib, especially in patients who have developed resistance to crizotinib. ^{1 2 3 6 9}

Research Team

Giovanni Selvaggi, MD

Principal Investigator

CEO

Eligibility Criteria

Adults with advanced ALK-positive NSCLC, who can swallow pills and have good organ function. They must not be pregnant or breastfeeding, agree to use contraception, and can't have had certain recent treatments or heart issues. Only one prior chemo regimen is allowed.

Inclusion Criteria

You are able to perform everyday activities without any problems or with only a little difficulty.

You can swallow and keep down pills or liquid medicine.

Life expectancy of at least 12 weeks.

Exclusion Criteria

You have tumors in your brain or spinal cord covering.

You are allergic to tartrazine, a dye used in the ensartinib 100 mg capsule.

Women who are pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either X-396 (ensartinib) or crizotinib until disease progression or unacceptable toxicity

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Crizotinib
• X-396 (Ensartinib)

Trial Overview The trial compares the effectiveness of a new drug called Ensartinib (X-396) against Crizotinib in treating ALK-positive NSCLC patients who've had limited previous chemotherapy but no prior ALK inhibitors.

Participant Groups

Group I: X-396 (ensartinib) Experimental Treatment 1 Intervention

Eligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops

Group II: crizotinib Active Control 1 Intervention

Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID with or without food until progression or unacceptable toxicity develops

Crizotinib is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in European Union as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Japan as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Approved in Canada as Xalkori for:

• Non-small cell lung cancer (NSCLC) with ALK rearrangements

Who Is Running the Clinical Trial?

Xcovery Holding Company, LLC

Lead Sponsor

Trials

9

Recruited

530+

Xcovery Holdings, Inc.

Lead Sponsor

Trials

10

Recruited

620+

Findings from Research

Crizotinib is a targeted therapy that has shown significant anticancer activity in patients with advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer, leading to its FDA approval in 2011.

This review highlights crizotinib's efficacy as a personalized treatment option compared to traditional chemotherapy for patients who have already undergone treatment for non-small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. Guo, L., Zhang, H., Shao, W., et al.[2018]

Crizotinib is an effective treatment for adults with ALK-rearranged non-small-cell lung cancer, but managing its common side effects is essential for maintaining treatment continuity and achieving optimal survival rates.

While some side effects like visual disturbances and bradycardia are generally mild, serious cardiac and liver-related adverse events require careful monitoring, particularly for QT interval prolongation and liver function, to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? Girard, N., Audigier-Valette, C., Cortot, AB., et al.[2018]

Crizotinib is an effective treatment for ALK-positive non-small cell lung cancer (NSCLC), showing a significant improvement in progression-free survival (PFS) compared to standard chemotherapy, with a median PFS of 7.7 months versus 3.0 months in the chemotherapy group during a study of 347 patients.

While crizotinib has a high response rate and was approved based on its efficacy, it also has notable side effects, including vision disorders and hepatotoxicity, highlighting the importance of monitoring for serious adverse reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. Kazandjian, D., Blumenthal, GM., Chen, HY., et al.[2022]

Crizotinib is an effective treatment for adults with ALK-positive advanced non-small cell lung cancer (NSCLC), showing significant improvements in progression-free survival and quality of life compared to standard chemotherapy in ongoing phase I/II and phase III studies involving previously treated patients.

The treatment is generally well tolerated, although it can cause liver transaminase elevations and neutropenia as common adverse events; however, the long-term survival benefit remains uncertain due to confounding factors in the data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. Frampton, JE.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Background and rationale of the eXalt3 trial investigating X-396 in the treatment of ALK+ non-small-cell lung cancer. [2019]

2. China pubmed.ncbi.nlm.nih.gov

[Pharmacology and Clinical Evaluation of Ensartinib Hydrochloride Capsule]. [2021]

3. Singapore pubmed.ncbi.nlm.nih.gov

Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial. [2021]

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

Crizotinib as a personalized alternative for targeted anaplastic lymphoma kinase rearrangement in previously treated patients with non-small-cell lung cancer. [2018]

5. China pubmed.ncbi.nlm.nih.gov

Ensartinib in advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, two-staged, phase 1 trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial. [2020]

7. England pubmed.ncbi.nlm.nih.gov

ALK-rearranged non-small cell lung cancers: how best to optimize the safety of crizotinib in clinical practice? [2018]

8. England pubmed.ncbi.nlm.nih.gov

FDA approval summary: crizotinib for the treatment of metastatic non-small cell lung cancer with anaplastic lymphoma kinase rearrangements. [2022]

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

Crizotinib: a review of its use in the treatment of anaplastic lymphoma kinase-positive, advanced non-small cell lung cancer. [2021]