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)

Plain English Summary

Neoadjuvant Therapy With Ensartinib Combined With Chemotherapy for ALK-positive Non - Small Cell Lung Cancer (NSCLC) is a Phase 2 clinical trial sponsored by Tang-Du Hospital studying NSCLC (Non-small Cell Lung Cancer). Tests if Ensartinib combined with chemotherapy can lead to a complete tumor removal after surgery for ALK-positive NSCLC. For patients with stage II-IIIB (N2) ALK-positive NSCLC, who are fit for surgery and have not received prior anti-tumor therapy. Participants will take Ensartinib (oral) and chemotherapy (Pemetrexed and Carboplatin) for 9 weeks, followed by surgery and regular check-ups. Alternative treatments include standard chemotherapy or targeted therapies, but this study focuses on the combination of Ensartinib and chemotherapy. The trial aims to enroll 20 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Aged 18-75, ALK-positive NSCLC, able to undergo surgery, no prior anti-tumor therapy, and no severe health issues. Excluded if pregnant, have squamous cell carcinoma, or have had previous exposure to other anti-tumor therapies. Must have adequate organ function and no severe systemic diseases. No history of interstitial lung disease or hypersensitivity to Ensartinib. This trial is studying NSCLC (Non-small Cell Lung Cancer), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the rate of pathological complete response, which means no detectable cancer in surgically removed tissue, a significant improvement in patient outcomes. The specific primary outcome measures are: Pathological complete response rate (pCR) (From enrollment to the end of treatment at 9 weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill the gap in understanding the effectiveness of Ensartinib combined with chemotherapy for ALK-positive NSCLC, potentially offering a new treatment option. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets NSCLC (Non-small Cell Lung Cancer), where improved treatment options are needed.

Investor Insight

The market for targeted therapies for ALK-positive NSCLC is growing, with this study potentially leading to a new approved treatment, making it an attractive investment opportunity. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you have ALK-positive NSCLC and are fit for surgery. Understand the treatment involves taking Ensartinib and chemotherapy for 9 weeks, followed by surgery and regular check-ups. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 20 participants

Interventions

• DRUG: Ensartinib + Chemotherapy — For patients with operable stage II - IIIB (N2) ALK - fusion - positive lung adenocarcinoma, after signing the informed consent form and being screened to meet the inclusion and exclusion criteria, they will receive treatment with ensartinib combined with pemetrexed and carboplatin for a duration of 9 weeks. Subsequently, after a comprehensive assessment, they will undergo surgical treatment. After the surgery, the pathological complete response rate (pCR), major pathological response rate (MPR)

Primary Outcomes

• Pathological complete response rate (pCR) (From enrollment to the end of treatment at 9 weeks)

Secondary Outcomes

• Major pathological response rate (MPR) (From enrollment to the end of treatment at 9 weeks)
• Objective Response Rate (ORR) (From enrollment to the end of treatment at 3 years)
• R0 Resection Rate (Evaluated immediately after surgical intervention)
• 3-year EFS Rate (Measured over a period of 3 years from study entry or treatment initiation)
• Event-Free Survival (EFS) (From enrollment to the end of treatment at 5 years)

Full 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.

Trial Locations

• Tangdu Hospital, Xi’an, Shanxi, China

Frequently Asked Questions

Related Conditions

• ALK-positive NSCLC, lung adenocarcinoma, non-small cell lung cancer, targeted therapy, chemotherapy

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