Neoadjuvant ensartinib plus chemotherapy for resectable ALK-positive NSCLC

A Single-arm, Multicenter Clinical Study of Ensartinib Combined With Chemotherapy as Neoadjuvant Therapy for ALK-positive Non-small Cell Lung Cancer (NSCLC) (TD-ENSEMBLE Study)

This will test whether taking ensartinib with chemotherapy before surgery helps people with stage II–IIIB (N2) ALK-positive, resectable non-small cell lung cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Tang-Du Hospital (Academic / other)
• Drugs / interventions: Ensartinib, chemotherapy, radiation, crizotinib, ceritinib, alectinib, brigatinib
• Locations: 1 site (Xi’an, Shanxi)
• Trial ID: NCT07354061 on ClinicalTrials.gov

What this trial studies

This is a single-arm phase 1/2 trial giving oral ensartinib combined with platinum-based doublet chemotherapy to adults with resectable stage II–IIIB (N2) ALK-positive lung adenocarcinoma prior to planned surgery. The design includes a two-stage safety run with an initial cohort of five participants and progression to stage two only if no unexpected serious adverse events related to ensartinib are observed. The main efficacy endpoint is pathological complete response (pCR) in surgically removed tumor tissue after neoadjuvant treatment, and safety and adverse events are closely tracked. All participants receive the investigational combination; there is no control arm.

Who should consider this trial

Good fit: Adults 18–75 with histologically confirmed, surgically resectable stage II–IIIB (N2) lung adenocarcinoma who test positive for ALK fusion, have ECOG performance status 0–1, and adequate organ function are ideal candidates.

Not a fit: Patients with ALK-negative tumors, unresectable or metastatic disease, poor performance status, or contraindications to chemotherapy or ensartinib are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, the combination could increase the chance of achieving a pathologic complete response at surgery and may improve long-term outcomes.

How similar studies have performed: ALK inhibitors are well established in advanced ALK-positive NSCLC, but using ensartinib as neoadjuvant therapy is novel and prior data on this specific approach are limited.

Eligibility criteria

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.

Where this trial is running

Xi’an, Shanxi

• Tangdu Hospital — Xi’an, Shanxi, China (Recruiting)

Study contacts

• Study coordinator: Yan xiaolong Doctor

Conditions NSCLC; Ensartinib; neoadjuvant; ALK - positive; Resectable