Efficacy and Safety of Ensartinib in Neoadjuvant Therapy for Stage IIA - IIIB (Operable or Potentially Operable) ALK-Positive Lung Adenocarcinoma ：A Multicenter, Real-World Clinical Study

January 19, 2025 updated by: Fujian Medical University Union Hospital

According to the Global Cancer Statistics 2022 report, lung cancer is the most common type of cancer (12.4% of the total) and the leading cause of cancer deaths (18.7% of total cancer deaths). According to the pathological classification of patients, lung cancer is divided into small cell lung cancer and non-small cell lung cancer, of which non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer.

Surgery is the preferred treatment for patients with early-stage lung cancer, according to the 2024 CSCO Guidelines. However, most patients have the possibility of recurrence and metastasis after surgery. The 5-year survival rate of patients with stage IA NSCLC is 80%-90%, but the 5-year survival rate of patients with stage ⅢB NSCLC drops to 40%. Neoadjuvant therapy has become an important part of the treatment of non-small cell lung cancer (NSCLC) in order to prolong the survival of patients.

In the past few years, many driver genes of NSCLC have been identified, and anaplastic lymphoma kinase (ALK) is one of them. ALK was first identified in anaplastic large cell lymphoma (ALCL). Studies at home and abroad have shown that ALK-rearranged (positive)NSCLC accounts for about 3%-7% of all NSCLC patients.

Many studies have suggested that ALK-TKI is clinically feasible as a neoadjuvant therapy for ALK positve patients with locally advanced NSCLC.

The investigators designed this study to explore the efficacy of enshatinib neoadjuvant therapy in patients with stage IIA to III ALK-positive lung adenocarcinoma

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

According to the Global Cancer Statistics 2022 report, lung cancer is the most common type of cancer (12.4% of the total) and the leading cause of cancer deaths (18.7% of total cancer deaths). The statistics of the National Cancer Center of China shows that there are about 1 061 thousand new cases and 733 thousand deaths of lung cancer in China every year, which account for the first incidence and mortality of malignant tumors in China. According to the pathological classification of patients, lung cancer is divided into small cell lung cancer and non-small cell lung cancer, of which non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer.

Surgery is the preferred treatment for patients with early-stage lung cancer, according to the 2024 CSCO Guidelines. However, most patients have the possibility of recurrence and metastasis after surgery. The 5-year survival rate of patients with stage IA NSCLC is 80%-90%, but the 5-year survival rate of patients with stage ⅢB NSCLC drops to 40%. Neoadjuvant therapy has become an important part of the treatment of non-small cell lung cancer (NSCLC) in order to prolong the survival of patients.

In the past few years, many driver genes of NSCLC have been identified, and anaplastic lymphoma kinase (ALK) is one of them. ALK was first identified in anaplastic large cell lymphoma (ALCL). Studies at home and abroad have shown that ALK-rearranged (positive)NSCLC accounts for about 3%-7% of all NSCLC patients.

Many studies such as The SAKULA study,The ALNEO Study have suggested that ALK-TKI is clinically feasible as a neoadjuvant therapy for ALK positve patients with locally advanced NSCLC.

Ensartinib is a novel potent and highly selective second-generation ALK inhibitor, which has a good selective inhibition effect on c-Met. Structurally, Ensartinib is similar to crizotinib, but Ensartinib has stronger binding to ALK and better selectivity than crizotinib, and both in vitro and in vivo experiments have shown the potential of ensartinib for crizotinib-resistant tumors.

The safety profile of ensartinib was manageable. In the eXalt3 study, the most common adverse events of all grades in the ensartinib group were rash, pruritus, and elevated aminotransferase (ALT, AST).

The eXalt3 study confirmed that first-line use of ensartinib can significantly improve mPFS compared with crizotinib in ALK-positive NSCLC patients, and ensartinib provides better efficacy and safety, making it a new first-line treatment option for ALK-positive NSCLC patients.

ALK inhibitors have brought great survival benefits to ALK-positive advanced NSCLC, but the exploration of ALK inhibitors in early-stage patients has just begun,with no authoritative results have been published. TThe investigators designed this study to explore the efficacy of neoadjuvant treatment with ensartinib in patients with stage IIA-IIB ALK-positive lung adenocarcinoma who had undergone neoadjuvant chemotherapy for ALK mutation.

The primary goal of this study is to evaluate the major pathological response (MPR) to neoadjuvant ensartinib in patients with resectable stage IIA to IIIb ALK-positive non-small cell lung cancer (NSCLC).

The secondary objectives are to evaluate the complete pathological response (pCR), objective response rate (ORR), and safety of neoadjuvant ensartinib in patients with resectable stage IIA-IIIb ALK-positive non-small cell lung cancer (NSCLC)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Fujian
      • Fuzhou, Fujian, China, 350100
        • Fujian Medical University Union Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥18
  • Histologically or cytologically confirmed lung adenocarcinoma
  • Evaluated resectable TNM stage IIA-IIIB (operable or potentially operable) non-small cell lung cancer (NSCLC)
  • Alk-positive as determined by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), or other non-specific sequencing methods，before treatment with ALK inhibitors
  • Measurable lesions were determined with the use of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria) on CT scans
  • Magnetic resonance imaging (MRI) or CT scans of the brain show no metastatic disease
  • Tumors contained components of squamous cell carcinoma, large-cell neuroendocrine carcinoma, or small-cell carcinoma
  • Severe infections, including COVID-19, including but not limited to hospitalization due to complications of infection within the 4 weeks prior to starting study treatment
  • Have not received chemotherapy, radiotherapy, or biological therapy
  • Hemoglobin ≥100 g/L(which can be maintained or exceeded by blood transfusion); Absolute neutrophil count ≥2.0×109/L; Platelet count ≥100×109/L
  • Total bilirubin ≤1.5 times upper limit of normal; ALT and AST≤2.5 times the upper limit of normal; CREA ≤1.5 times the upper limit of normal and CREA clearance ≥60mL/min
  • Women of childbearing age (15 to 49 years) must undergo a urine pregnancy test within 7 days before starting treatment and the result is negative
  • Informed consent is obtained from patients or their legal representatives
  • Able to swallow oral medications normally
  • ECOG behavior status score is 0 to 1
  • Men and women of reproductive age agree to use a reliable method of contraception before entering the trial, during the study and up to eight weeks after discontinuation
  • Stable health status, including no acute exacerbations of chronic diseases, serious infections, or major surgeries during the first 4 weeks of enrollment, as indicated in other inclusion/exclusion criteria

Exclusion Criteria:

  • Have received any systemic anti-cancer treatment for locally advanced non-small cell lung cancer, including chemotherapy, biotherapy (including ALK-TKI), immunotherapy, or any investigational drug
  • PET-CT scan or biopsy results showing unresectable stage III and IV disease with distant metastasis (including malignant pleural effusion)
  • Patients who had a cancer other than NSCLC within 5 years before the initiation of study treatment
  • Allergy to ensartinib or any of the ingredients in this product
  • Previous history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonia requiring hormone therapy, or any clinically proven active interstitial lung disease;Baseline CT scans found idiopathic pulmonary fibrosis
  • Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow preparations, or previous major bowel resection resulting in inadequate absorption of ensartinib
  • Any unstable systemic illness, including active infection, uncontrolled hypertension, unstable angina, angina with onset within the last 3 months, congestive heart failure (≥ New York Heart Association [NYHA] class II), myocardial infarction (within 6 months before enrollment), severe arrhythmias requiring medical therapy, or hepatic, renal, or metabolic disease
  • Human immunodeficiency virus (HIV) infection
  • Pregnant or lactating women
  • A definite past history of neurological or psychiatric disorders, including epilepsy or dementia
  • History of organ transplantation
  • Rheumatic immune-related diseases
  • Other cases that the researcher deemed unsuitable for enrollment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ensartinib For Neoadjuvant Therapy
receive neoadjuvant treatment with ensartinib 225 mg once a day, po. for 2 consecutive cycles (56 days) to evaluate possibility of surgery, or discontinue the treatment because of disease recurrence or intolerable toxicity
Drug: Ensartinib
receive neoadjuvant treatment with ensartinib 225 mg once a day, po. for 2 consecutive cycles (56 days) to evaluate possibility of surgery, or discontinue the treatment because of disease recurrence or intolerable toxicity

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Major pathological response rate(MPR)
Time Frame: From enrollment to the end of treatment at 8 weeks
The proportion of patients with ≤10% residual viable tumor cells in the resected primary tumor and metastatic lymph nodes after completion of neoadjuvant therapy
From enrollment to the end of treatment at 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pathological complete response rate (pCR)
Time Frame: From enrollment to the end of treatment at 8 weeks
Proportion of patients who had no residual tumor in the resected primary tumor and metastatic lymph nodes after completion of neoadjuvant therapy
From enrollment to the end of treatment at 8 weeks
Objective Response Rate (ORR)
Time Frame: From enrollment to the end of treatment at 8 weeks
The proportion of patients with a complete response (CR) or partial response (PR) among all patients, as assessed according to RECIST, version 1.1
From enrollment to the end of treatment at 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fujian Medical University Union Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 26, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2024ENT01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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