Ensartinib vs. Crizotinib for Non-Small Cell Lung Cancer

Not currently recruiting at 146 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, ensartinib and crizotinib (also known as Xalkori), to determine which is more effective and safer for individuals with ALK-positive non-small cell lung cancer. Participants must have this specific type of lung cancer, must not have taken any ALK inhibitor treatments before, and must have undergone only one round of chemotherapy. The study aims to improve treatment options for those who meet these criteria and to help manage their cancer more effectively. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that ensartinib, also known as X-396, is generally well-tolerated by patients with ALK-positive non-small cell lung cancer (NSCLC). One study found that ensartinib has manageable safety, and the FDA recently approved it for treating this type of cancer, indicating it has passed strict safety checks.

For crizotinib, studies have demonstrated its effectiveness and relative safety for people with ALK-positive NSCLC. More than 90% of patients experienced tumor shrinkage, and safety data from real-world studies also support its use.

Both treatments, ensartinib and crizotinib, have undergone safety studies in people. While both have common side effects typical of cancer treatments, their approval and ongoing research highlight their safety profiles. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for non-small cell lung cancer (NSCLC) with ALK rearrangements, like crizotinib, work by blocking the ALK protein to stop cancer cell growth. However, ensartinib stands out because it is designed to bind more effectively to the ALK protein, potentially overcoming resistance that develops with other ALK inhibitors. Researchers are excited about ensartinib because it has shown promise in crossing the blood-brain barrier, which could be crucial for treating or preventing brain metastases common in ALK+ NSCLC patients. This new approach might offer hope for patients whose cancers have stopped responding to existing treatments.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer?

This trial will compare ensartinib and crizotinib for ALK-positive non-small cell lung cancer (NSCLC). Research has shown that ensartinib is effective for this type of cancer, leading to FDA approval due to strong confidence in its efficacy. Ensartinib targets the ALK protein that aids cancer cell growth and has shown promise in shrinking tumors.

Crizotinib, another treatment option in this trial, also demonstrates strong results for ALK-positive NSCLC. Studies have found that it can shrink tumors in over 90% of patients and more than double the time patients live without cancer progression compared to chemotherapy. Both treatments offer hope for effectively managing ALK-positive NSCLC. ^{1 2 3 5 6}

Who Is on the Research Team?

Giovanni Selvaggi, MD

Principal Investigator

CEO

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3936578/

Activity and safety of crizotinib in patients with ALK-positive ... In the ALK-positive lung cancer population within this study, crizotinib showed marked efficacy, with tumour shrinkage in over 90% of patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0169500224003507

Efficacy and safety of crizotinib in the treatment ... Meta-analysis of 14 crizotinib aNSCLC RWE studies yielded a pooled ORR of 70.6 %, median rwPFS of 14.5 mo, and OS of 40.2 mo. •. The real-world safety and ...

3. cancer.gov cancer.gov/types/lung/research/crizotinib

Crizotinib for Advanced Non-Small Cell Lung Cancer - NCI Results. Progression-free survival was more than twice as long in patients treated with crizotinib than in those who received chemotherapy: 7.7 ...

4. pfizer.com pfizer.com/news/press-release/press-release-detail/pfizer_presents_overall_survival_data_of_xalkori_in_patients_with_alk_positive_advanced_non_small_cell_lung_cancer

Pfizer Presents Overall Survival Data of XALKORI in ... After a median follow-up of 46 months, the median OS for patients randomized to XALKORI was not reached (95% CI: 45.8 months, not reached) and ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00581

Lorlatinib Versus Crizotinib in Patients With Advanced ALK ... After 5 years of follow-up, lorlatinib continued to show superior efficacy over crizotinib in patients with advanced ALK-positive non–small cell ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/30/23/5323/750203/Safety-Efficacy-and-Biomarker-Analysis-of

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET ... MET mutations, present in 3% to 4% of advanced non–small cell lung cancer cases, correlate with poor survival. Despite known sensitivity to c- ...