Neoadjuvant Ensartinib in ALK Positive Resectable Stage II to III Non-Small Cell Lung Cancer

A Study of Ensartinib as Neoadjuvant Therapy for Patients With ALK Positive Resectable Stage II to III Non-Small Cell Lung Cancer：A Prospective, Open-label, Multi-center, Single-arm, Phase II Clinical Trial

This single-arm, prospective, multicenter, phase II study is designed to evaluate the efficacy and safety of ensartinib as neoadjuvant treatment in ALK positive, resectable for stage II to III non-small cell lung cancer patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Ensartinib

Detailed Description

This is a single-Arm, prospective, multicenter, phase II study, the primary endpoint is pathological complete response (pCR). Participants will receive ensartinib at 225 mg orally once a day taken with or without food for 12 weeks before surgical resection.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qinghua Zhou; Phone Number: 028-85422114; Email: Prof._QH.Zhou_GCP@wchscu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Give written informed consent before any study procedure.
2. Male or female aged between 18 and 75 years old (including 18 and 75 years old).
3. Histologically or cytologically documented lung adenocarcinoma within 60 days prior to study enrollment.
4. Clinical stage II-III assessed by EBUS-TBNA or PET/CT can be resected.
5. Patients confirmed as ALK fusion positive by RBK (NGS) test.
6. Presence of at least one accurately measurable lesion, CT showing a maximum diameter of 10mm at baseline (except for lymph nodes with a short axis of 15mm required) and suitable for accurate repeat measurements.
7. Eastern Cooperative Oncology Group (ECOG) performance status （PS） of 0 or 1.

8. Adequate hematological, biochemical and organ functions, defined as follows

   1. Hemoglobin ≥90g/L. Note: transfusions are allowed to meet the required hemoglobin level;
   2. Absolute neutrophil count (ANC) ≥1.5× 10^9/L
   3. Platelets ≥90 × 10^9/L;
   4. Total bilirubin ≤ 2 times the 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. Cardiopulmonary function suitable for surgical treatment (ECG, echocardiography, pulmonary function or blood gas analysis);

10. At least 2 weeks prior to initial trial treatment female subjects should use adequate contraceptive measures, the pregnancy test must be negative and there is no ongoing breastfeeding. Otherwise, one of the following criteria must be met during screening to prove the possibility of no fertility:

    1. Postmenopausal is defined as amenorrhea for at least 12 months after stopping all exogenous hormone treatment over 50 years old;
    2. Women under the age of 50 should be regarded as menopause if they stop menopause for 12 months or more after stopping exogenous sex hormone therapy, and their LH and FSH levels are within the postmenopausal range of the institution;
    3. Irreversible surgical sterilization recorded by hysterectomy, bilateral oophorectomy or bilateral salpingectomy, but excluding tubal ligation.
11. Men with partners of childbearing potential willing to use adequate contraceptive measures during the study and for 3 months after the last dose of study medication.

Exclusion Criteria:

1. Mixed squamous cell carcinoma, large cell neuroendocrine carcinoma or small cell lung cancer;
2. Prior treatment with any anti-cancer therapy;
3. Pregnant female patients; breastfeeding female patients.
4. Current use of (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior). All patients must try to avoid using or ingesting any drugs, herbal supplements and/or foods that are known to have induced effects on CYP3A4.
5. Evidence of any severe or uncontrolled systemic disease, including uncontrolled hypertension and active bleeding, that the investigator considers to be detrimental to patient participation in the study or to adherence to the protocol. Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) or known human immunodeficiency virus (HIV). Screening for chronic diseases is not a requirement.
6. Past medical history of Interstitial lung disease（ILD）, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
7. A history of hypersensitivity to active or inactive excipients of Ensartinib or to drugs of similar chemical structure or class to Ensartinib, and uncontrollable nausea and vomiting, chronic gastrointestinal disease, inability to swallow drugs, or had undergone major bowel resection that would interfere with adequate absorption of Ensartinib.

8. Any of the following cardiac criteria:

   1. Mean resting corrected QT interval (QTc)>470 msec, obtained from 3 electrocardiograms (ECGs)
   2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third-degree heart block, second-degree heart block.
   3. Any factors that increase the risk of QTc prolongation or the risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
9. A clear past history of neurological or psychiatric disorders, including epilepsy or dementia；
10. Other circumstances deemed inappropriate by the investigator for participation in the 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; Ensartinib 225 mg oral once daily 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR) rate	pCR rate is defined as the proportion of participants who have achieved pathologic complete response (with no residual viable tumor in lung primary or lymph nodes as evaluated by central pathology laboratory of surgical specimens) in all participants.	Within 2 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Pathological Response (MPR) rate	MPR rate is defined as the proportion of participants who have achieved major pathologic response (less than or equal to 10% of residual viable tumor in lung primary or lymph nodes as evaluated by central pathology laboratory of surgical specimens) in all participants.	Within 2 month after surgery
Objective Response Rate (ORR)	ORR was defined as the percentage of participants who attained complete response (CR) or partial response (PR). Responses are according to RECIST 1.1 as assessed by investigator.	Pre-operation
Incidence of Adverse Events	Toxicity will be graded by NCI Common Terminology Criteria for Adverse Events (CTCAE version 5.0)	Up to 1 month after surgery
Disease free survival (DFS)	DFS is defined as the time from the first day after radical surgery until the first date of disease recurrence (local or distant) or date of death due to any cause, whichever occurs first.	3 years postoperatively
Overall Survival (OS)	OS was defined as the time from the date of enrollment to death from any cause.	5 years postoperatively

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 15, 2025
• Primary Completion (Estimated): June 12, 2028
• Study Completion (Estimated): December 12, 2030

Study Registration Dates

• First Submitted: January 11, 2025
• First Submitted That Met QC Criteria: January 11, 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: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: CLOG-0003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No