Neoadjuvant Therapy With Ensartinib Combined With Chemotherapy for ALK-positive Non - Small Cell Lung Cancer (NSCLC)

Summary

The goal of this clinical trial is to learn if Ensartinib combined with chemotherapy works as a neoadjuvant treatment for patients with stage II-IIIB (N2) ALK-positive non-small cell lung cancer (NSCLC). It will also learn about the safety of this combination therapy. The main questions it aims to answer are: * Does Ensartinib combined with chemotherapy lead to a pathological complete response (pCR) in surgically removed tumor tissue after neoadjuvant treatment? * What medical problems do participants have when taking Ensartinib combined with chemotherapy? This is a single-arm study, meaning all participants will receive the investigational treatment. There is no placebo or active comparator group. The study will be conducted in two stages; the second stage will proceed only if no special, unexpected, or serious adverse events related to Ensartinib occur during the first stage involving 5 participants. Participants will: * Receive neoadjuvant treatment with Ensartinib (taken orally once daily) plus Pemetrexed and Carboplatin (administered intravenously every 3 weeks) for 9 weeks (3 cycles). * Undergo surgical resection within 4 weeks after completing neoadjuvant therapy. * Attend regular clinic visits for check-ups, blood tests, and imaging scans (CT, MRI) according to a detailed schedule during the neoadjuvant, surgical, and long-term follow-up periods (up to 10 years). * Be monitored for adverse events and survival outcomes.

Eligibility

Inclusion Criteria:

1. Provide informed consent prior to any study-specific procedures.
2. Aged between 18 and 75 years old (inclusive).
3. Histologically or cytologically confirmed lung adenocarcinoma via biopsy performed within 60 days prior to study enrollment.
4. Surgically resectable Stage II-IIIB (N2) lung adenocarcinoma (AJCC 8th Edition TNM Staging).
5. Confirmed ALK fusion mutation by detection methods recommended by NCCN guidelines.
6. Presence of at least one accurately measurable lesion, with the longest diameter ≥10 mm on baseline computed tomography (CT) scan (or lymph nodes with a short axis ≥15 mm) and suitable for accurate repeated measurements.
7. ECOG performance status of 0-1.
8. Adequate hematological, biochemical, and organ function:

   1. Hemoglobin ≥90 g/L (can be maintained or exceeded via transfusion);
   2. Absolute neutrophil count ≥1.5×10⁹/L;
   3. Platelet count ≥90×10⁹/L;
   4. Total bilirubin ≤2× upper limit of normal (ULN);
   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN;
   6. Creatinine ≤1.5× ULN; and creatinine clearance ≥60 mL/min.
9. Adequate cardiopulmonary function suitable for surgical treatment (assessed by ECG, echocardiography, pulmonary function tests, or blood gas analysis).
10. For female subjects of childbearing potential: Must use highly effective contraception for at least 2 weeks prior to initiation of study drug, have a negative pregnancy test, and not be breastfeeding at the start of dosing. Alternatively, must meet one of the following criteria at screening to demonstrate non-childbearing potential:

    1. Postmenopausal, defined as over 50 years old with amenorrhea for at least 12 months following cessation of all exogenous hormonal therapy.
    2. Women under 50 years old may be considered postmenopausal if they have amenorrhea for 12 months or more following cessation of exogenous hormone therapy and have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the postmenopausal range.
    3. Documented irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not including tubal ligation.
11. For male subjects with partners of childbearing potential: Must agree to use effective contraceptive methods during the study period and for 3 months after the last dose of study drug

Exclusion Criteria:

1. Presence of squamous cell carcinoma, large cell neuroendocrine carcinoma, or small cell carcinoma components.
2. Prior exposure to other anti-tumor therapies before enrollment.
3. Patient is pregnant or breastfeeding.
4. Current use of (or inability to discontinue use at least 3 weeks prior to receiving the first dose of study treatment) drugs or herbal supplements known to be strong inducers of CYP3A4. All patients must try to avoid concomitant use or ingestion of any drugs, herbal supplements, and/or foods known to have CYP3A4 induction effects.
5. Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding, which in the investigator's opinion would compromise the patient's participation in the study or protocol compliance, or active infections including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
6. Prior history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any current evidence of active ILD.
7. History of hypersensitivity to active or inactive excipients of Ensartinib or drugs with similar chemical structures or classes to Ensartinib, as well as uncontrollable nausea and vomiting, chronic gastrointestinal diseases, inability to swallow formulated medication, or prior extensive bowel resection that would preclude adequate absorption of Ensartinib.
8. Intolerance to chemotherapy or refusal of chemotherapy.
9. Any of the following cardiac criteria:

   1. Mean resting corrected QT interval (QTc) \> 470 msec obtained from three ECGs using the screening ECG machine's QTc value.
   2. Any clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG, such as left bundle branch block, third-degree heart block, or second-degree heart block.
   3. Any factors that increase the risk of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death under 40 years of age in first-degree relatives, or any concomitant medication known to prolong the QT interval.
10. History of definite neurological or psychiatric disorders, including epilepsy or dementia.
11. Any other conditions deemed by the investigator as unsuitable for enrollment.

Conditions3

Interventions1

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