Adjuvant Treatment of ALK-positive Non-small Cell Lung Cancer with Ensartinib Guided by MRD

Postoperative Adjuvant Treatment of ALK-positive Non-small Cell Lung Cancer with Ensartinib Guided by MRD: a Single-arm, Multicenter Study

To explore the efficacy and safety of ensartinib on adjuvant therapy guided by MRD in IA3-IIIB (T3N2) stage ALK-positive non-small cell lung cancer patients.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC, Stage I, II, IIIA, IIIB
• Intervention / Treatment: Drug: Ensartinib

Detailed Description

Eligible subjects will take ensartinib 225 mg once daily. Postoperative tissues will be collected for customized minimal residual disease (MRD) detection (tumor-informed MRD). MRD tests will be conducted within 14 to 50 days after surgery (before adjuvant therapy), every 12 weeks ± 7 days for the first two years, and every 24 weeks ± 7 days for the third year. Subjects with negative MRD after surgery will receive ensartinib treatment. If MRD turns positive, they will receive ensartinib 225 mg QD combined with platinum-based doublet chemotherapy (2 to 4 cycles) as a step-up treatment. Subjects with positive MRD after surgery will also receive ensartinib treatment. If MRD remains positive at the next MRD test, they will receive ensartinib 225 mg QD combined with platinum-based doublet chemotherapy (2 to 4 cycles) as a step-up treatment. If MRD turns negative during treatment, ensartinib monotherapy will be resumed. If MRD turns positive again, the subsequent treatment mode will be determined by the MDT discussion group composed of the main center researchers, including but not limited to monotherapy or combination with platinum-free chemotherapy until 3 years, or MRD turns negative, or intolerable toxicity, or radiological recurrence, whichever occurs first. For patients who remain MRD positive after 3 years of treatment, the MDT group will discuss the next steps.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Nan Wu; Phone Number: +86-010-88196391; Email: nanwu@bjmu.edu.cn
• Study Contact Backup: Name: Shi Yan; Email: dryanshi@outlook.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Cancer Hospital
      • Contact: Nan Wu; Phone Number: +86-010-88196391; Email: nanwu@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed primary non-small cell lung cancer;
2. Age ≥18 years old, gender unlimited;
3. The stage of the disease was based on AJCC/UICC 8th edition of lung cancer staging criteria; Complete surgical resection (R0) of primary lung cancer with Stage IA3 with high-risk recurrence factors, stage IB, II, IIIA, and IIIB (T3N2M0 only) of non-small cell lung were pathological confirmed;
4. Full recovery from surgery;
5. The biopsy or postoperative tumor tissue samples tested by the local laboratory are positive for ALK, and can be accepted by IHC, RT-PCR, FISH and NGS test results;
6. Intended to receive enshatinib postoperative adjuvant therapy;
7. ECOG physical status score is 0-1;
8. Has good hematopoietic and organ function, and the laboratory test values;
9. Participants with active hepatitis B or hepatitis C are allowed to be enrolled, provided that they receive strict antiviral therapy prior to medication and that liver function is adequate;
10. Syphilitic positive subjects are allowed to be enrolled, but strictly standardized anti-syphilis therapy is required before medication and syphilitic heart disease and other serious complications are excluded;
11. Fertile female subjects must have a negative serum pregnancy test at the time of screening and during at the end of the study; Male subjects whose partners are women of reproductive age should be surgically sterilized, or effective methods of contraception should be given during and at the end of the study;
12. Sign informed consent, voluntarily and be able to comply with the procedures of the trial and follow-up.

Exclusion Criteria:

1. Participating in a clinical study and receiving investigational drug therapy or investigational device within 4 weeks prior to initial dosing; If involved in non-interventional clinical trials can be included in this study;
2. There is unresectable or metastatic disease, pathology report showing microscopic positive surgical margin or extranodal invasion.
3. History of other malignancies within 5 years prior to the first dose of the study drug, except for malignancies that are expected to be cured after treatment (including but not limited to fully treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated with radical surgery);
4. Previous treatment for NSCLC, including chemotherapy (preoperative chemotherapy treatment ≤ 2 cycles is allowed), targeted therapy (such as small molecule tyrosine kinase inhibitors targeting EGFR, ALK, VEGFR and other pathways, monoclonal antibodies, etc.), immunotherapy, investigational therapy, etc.;
5. The subject has undergone major surgery within 3 weeks prior to the first dose of the study drug (including primary tumor surgery, thoracotomy, laparotomy, excluding vascular access establishment procedures);
6. Use of traditional Chinese medicine and Chinese medicine preparations with anti-tumor treatment indications or auxiliary therapeutic effects on tumors within 14 days prior to the first dose of the study drug;
7. Received strong CYP3A inhibitors or inducers and narrow therapeutic index CYP3A substrates within 14 days before the first dose of the study drug;
8. Clinically significant cardiovascular diseases；
9. Severe active infection, interstitial lung disease / pneumonia, or any other serious underlying disease that may affect the subject's acceptance of protocol treatment within 2 weeks before the first dose;
10. Positive HIV antibody test result;
11. Active pulmonary tuberculosis;
12. Pregnant or lactating women;
13. Any other clinically significant disease or condition that the investigator believes may affect protocol compliance or the subject's signing of the informed consent form, or is not suitable for participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ensartinib

Drug: Ensartinib; Patients will receive Ensartinib 225mg QD by MRD test guided, if MRD test shows negative, only ensartinib will be given. if MRD test turns from negative to posive, patients will receive step-up treatment, which is ensartibe plus platinum - based doublet chemotherapy no more than 4 cycles. If MRD test turns from posive to negative, only ensartinib will be given. if MRD test constantly shows positive, MDT will determine the next step ensartib-based therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	From enrollment to until the date of first documented progression or date of death from any cause, whichever came first	From enrollment to until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	adverse events using common terminology criteria for adverse events 5.0	From enrollment to until the date up to 60 months

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Collaborators: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): January 15, 2029
• Study Completion (Estimated): January 15, 2030

Study Registration Dates

• First Submitted: December 29, 2024
• First Submitted That Met QC Criteria: January 15, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 15, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: adjuvant therapy; NSCLC; ALK positive; MRD
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: BD-EN-IV025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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