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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Pathological complete response rate (pCR)
研究概览
简要总结
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.
详细描述
The TD - ENSEMBLE Study: A Single - Arm, Multicenter Clinical Trial on Neoadjuvant Therapy with Ensartinib Combined with Chemotherapy for ALK - Positive NSCLC
Research Background
This is a clinical trial initiated by researchers. It aims to deeply analyze the current treatment landscape of non - small cell lung cancer (NSCLC), focusing on the unmet clinical needs of specific molecular subtype patient groups, and then conduct a study on the neoadjuvant therapy of ensartinib combined with chemotherapy for ALK - positive NSCLC.
Lung cancer is the leading cause of cancer - related deaths worldwide, and NSCLC accounts for approximately 80% of all lung cancer cases. For patients initially diagnosed with locally advanced (Stage II - III) NSCLC, surgical resection is a potentially curative treatment. However, even if the surgery is successful, the long - term survival rate of patients remains unsatisfactory. The 5 - year overall survival rate of patients with Stage II - IIIA NSCLC is about 36% to 60%. To improve the prognosis, platinum - based double - drug chemotherapy has become one of the standard treatment regimens for peri - operative (including neoadjuvant and adjuvant therapy) operable NSCLC. Large - scale meta - analyses have shown that compared with surgery alone, pre - operative neoadjuvant chemotherapy can increase the absolute 5 - year survival rate by about 5% and reduce the relative risk of death by 13%. However, the magnitude of this benefit is limited, indicating the need to explore more effective treatment strategies.
The study focuses on patients with NSCLC who have a positive anaplastic lymphoma kinase (ALK) fusion gene, which accounts for about 3% to 7% of all NSCLC cases. The development of ALK tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm for advanced ALK - positive NSCLC. From the first - generation crizotinib to the subsequent second - and third - generation drugs, they have brought significant survival improvements for advanced patients. The study drug, ensartinib, is a second - generation ALK - TKI independently developed in China. It can not only strongly inhibit ALK but also has an inhibitory effect on the c - Met kinase. Clinical studies have shown that ensartinib has good efficacy in patients with advanced ALK - positive NSCLC who are resistant to crizotinib (the objective response rate (ORR) evaluated by independent review was 52%), and it has been approved for this indication. In the international multicenter Phase III eXalt3 study for first - line treatment, ensartinib significantly prolonged the median progression - free survival (mPFS was 31.3 months vs. 12.7 months) compared with crizotinib and has also been approved for first - line treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide informed consent prior to any study-specific procedures.
- •Aged between 18 and 75 years old (inclusive).
- •Histologically or cytologically confirmed lung adenocarcinoma via biopsy performed within 60 days prior to study enrollment.
- •Surgically resectable Stage II-IIIB (N2) lung adenocarcinoma (AJCC 8th Edition TNM Staging).
- •Confirmed ALK fusion mutation by detection methods recommended by NCCN guidelines.
- •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.
- •ECOG performance status of 0-
- •Adequate hematological, biochemical, and organ function:
- •Hemoglobin ≥90 g/L (can be maintained or exceeded via transfusion);
- •Absolute neutrophil count ≥1.5×10⁹/L;
- •Platelet count ≥90×10⁹/L;
- •Total bilirubin ≤2× upper limit of normal (ULN);
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5× ULN;
- •Creatinine ≤1.5× ULN; and creatinine clearance ≥60 mL/min.
- •Adequate cardiopulmonary function suitable for surgical treatment (assessed by ECG, echocardiography, pulmonary function tests, or blood gas analysis).
- •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:
- •Postmenopausal, defined as over 50 years old with amenorrhea for at least 12 months following cessation of all exogenous hormonal therapy.
- •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.
- •Documented irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not including tubal ligation.
- •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
排除标准
- •Presence of squamous cell carcinoma, large cell neuroendocrine carcinoma, or small cell carcinoma components.
- •Prior exposure to other anti-tumor therapies before enrollment.
- •Patient is pregnant or breastfeeding.
- •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 CYP3A
- •All patients must try to avoid concomitant use or ingestion of any drugs, herbal supplements, and/or foods known to have CYP3A4 induction effects.
- •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.
- •Prior history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any current evidence of active ILD.
- •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.
- •Intolerance to chemotherapy or refusal of chemotherapy.
- •Any of the following cardiac criteria:
- •Mean resting corrected QT interval (QTc) > 470 msec obtained from three ECGs using the screening ECG machine's QTc value.
- •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.
- •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.
- •History of definite neurological or psychiatric disorders, including epilepsy or dementia.
- •Any other conditions deemed by the investigator as unsuitable for enrollment.
结局指标
主要结局
Pathological complete response rate (pCR)
时间窗: From enrollment to the end of treatment at 9 weeks
次要结局
- 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)
- 5-year OS Rate(Measured over a period of 5 years from study entry or treatment initiation.)
- Overall Survival (OS)(From enrollment to the end of treatment at 5 years)
- 10-year OS Rate(Measured over a period of 10 years from study entry or treatment initiation.)
- Adverse events(from date of enrollment until the end of the study, assessed up to 60 months)