A Study Comparing Ensatinib Versus Platinum-Based Chemotherapy as Adjuvant Treatment for Stage II-IIIA ALK -Positive Non-Small Cell Lung Cancer

A Phase II, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Ensatinib Versus Platinum-Based Chemotherapy as Adjuvant Treatment for Stage II-IIIA ALK -Positive Non-Small Cell Lung Cancer

This randomized, active-controlled, multicenter, open-label, Phase II study is designed to evaluate the efficacy and safety of ensatinib compared with Platinum-Based Chemotherapy as adjuvant treatment in ALK fusion positive II-IIIA stage non-small cell lung cancer after surgical resection

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer; ALK Fusion Protein Expression; Adjuvant Therapy
• Intervention / Treatment: Drug: Ensatinib; Drug: chemotherapy

Detailed Description

Participants in the experimental arm will receive Ensatinib at 225 mg orally once a day (QD) taken with food for 2 years. Participants in the control arm will receive one of the protocol specified platinum based chemotherapy regimens for 4 cycles. Treatments will continue until disease recurrence, meeting one of treatment discontinuation criteria (eg, patient decision, adverse event, pregnancy), or achieving a maximum treatment duration of 2 years. At the time of disease recurrence, participants will enter a survival follow-up until death, withdrawal of consent or study closure, whichever occurs earlier.

• Study Type: Interventional
• Enrollment (Anticipated): 152
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: You Lu, MD; Phone Number: +8618980601763; Email: radyoulu@hotmali.com
• Study Contact Backup: Name: Yang Yu, MM; Phone Number: +8618030478269; Email: 18030478269@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Surgical resection of histologically confirmed Stage IIA to IIIA NSCLC with negative margins, ,within 10 weeks after the operation
• Documented ALK-positive disease according to FISH , Ventana IHC ,RT-PCR or NGS
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1
• At least 3-months life expectancy
• Adequate organ function
• Any major surgery should be completed at least 4 weeks before the first study drug treatment. Minor surgery/procedures must be completed at least 2 weeks before taking medication.
• Willingness and ability to comply with the trial and follow-up procedures
• Written informed consents are required to indicate that the patients are aware of the investigational nature of the study

Exclusion Criteria:

• More than 10 weeks before surgery Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal cell carcinoma or cervical cancer in situ
• Use of other investigational drug within 4 weeks prior to the first dose of Ensartinib
• Prior stem cell or organ transplant
• severe cardiovascular disease
• Presence of active gastrointestinal (GI) disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of Ensartinib
• Active hepatitis B, hepatitis C virus antibody positive, HIV virus antibody, Treponema pallidum antibody positive
• History of interstitial lung disease, drug-induced interstitial lung disease, history of radiation pneumonitis requiring steroid therapy, or any clinical signs of active interstitial lung disease
• Reproductive or pregnant or breastfeeding female with a positive serum pregnancy test 7 days before starting treatment , Male or female patients failure to take effective contraceptive measures or plan to give birth during the entire treatment period and 3 months after treatment ends
• Patients with a known allergy or delayed hypersensitivity reaction to drugs chemically related to ensartinib or to the active ingredient of ensartinib
• History of drug allergy, such as a history of allergies to pemetrexed, carboplatin or other platinum compounds, or their preventive medications; History of allergies to paclitaxel components; or uncontrolled asthma
• Patients who have used the following drugs within 14 days before the first dose or who need to use the following drugs during treatment: drugs that cause QTc prolongation and/or torsade de pointes-type ventricular tachycardia; strong inhibitors or strong inducers of CYP3A
• Patients being treated with warfarin or any other coumarin derivative anticoagulant
• According to the judgment of the investigator, other severe, acute or chronic medical conditions that may increase the risk associated with participating in the study, or may interfere with the interpretation of the study results
• Concurrent condition evaluated by investigator that would make it inappropriate for the patient to be enrolled

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ensatinib; 225 mg administered once daily orally for two years.	Drug: Ensatinib; 225 mg administered once daily orally for two years.; Other Names: X-396
Active Comparator: Platinum-Based Chemotherapy; Patients in the chemotherapy group were allowed to cross into the Ensatinib treatment group after the disease progressed.	Drug: chemotherapy; Pemetrexed : Participants will receive 500 mg/m^2, day 1 , Q21D , until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. Cisplatin :Participants will receive 75 mg/m^2, day 1 , 21 days/cycle, Q21D , until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. Paclitaxel: Participants will receive 175 mg/ m^2, day 1 , 21 days/cycle, Q21D , until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first. carboplatin AUC= 5 mg/ mL/min, intravenously guttae, day 1 ,Q21D ，until completion of treatment period (4 cycles), recurrence of disease, unacceptable toxicity, withdrawal of consent, or death, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival (DFS)	From date of randomization until date of the first observation of tumor recurrence, metastasis (based on imaging ) or death, up to approximately 5 years.

Secondary Outcome Measures

Outcome Measure	Time Frame
DFS at 2 years	Assessed at 2 years
DFS at 3 years	Assessed at 3 years
Overall survival (OS)	The time from the date of randomization to death from any cause, up to approximately 7 years
OS rate at 5 years	Assessed at 5 years

Collaborators and Investigators

• Sponsor: Sichuan University
• Collaborators: Betta Pharmaceuticals Co., Ltd.
• Investigators: Study Chair: You Lu, MD, Sichuan University; Study Chair: Meijuan Huang, MD, Sichuan University

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): December 15, 2025
• Study Completion (Anticipated): December 20, 2028

Study Registration Dates

• First Submitted: December 29, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BD-EN-IV005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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