Ensartinib as Adjuvant Treatment in Anaplastic Lymphoma Kinase (ALK) Positive Non-small Cell Lung Cancer

A Phase Ⅲ, Double-blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of Ensartinib Versus Placebo as Adjuvant Therapy in Patients With Anaplastic Lymphoma Kinase (ALK)-Positive Stage IB- IIIB Non-small Cell Lung Cancer.

This double-blind, randomized, placebo-controlled, multicenter, Phase III study is designed to evaluate the efficacy and safety of ensatinib compared with placebo as adjuvant treatment in ALK positive stage II-IIIB non-small cell lung cancer after surgical resection with or without chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Ensartinib; Drug: Placebo

Detailed Description

This is a double-blind, randomized, placebo-controlled, multicenter, Phase III study, the primary endpoint is disease-free survival. Participants in the experimental arm will receive Ensatinib at 225 mg orally once a day taken with or without food for 2 years. Participants in the control arm will receive placebo at 225 mg orally once a day taken with or without food for 2 years. 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, whichever occurs earlier. At the time of treatment discontinuation, participants will enter a survival follow-up until death, withdrawal of consent or study closure, whichever occurs earlier.

• Study Type: Interventional
• Enrollment (Estimated): 202
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chang Li Wang, Ph.D; Phone Number: 3180 86-22-23340123; Email: wangchangli@tjmuch.com

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Chang Li Wang, Ph.D; Phone Number: 3180 86-22-23340123; Email: wangchangli@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of primary non-small cell carcinoma of the lung.
• Patients must be classified post-operatively as Stage IB-IIIB(T3N2M0) on the basis of pathologic criteria after complete surgical resection(R0).
• Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.
• Confirmation by the central laboratory that the tumour harbours ALK positive.
• At least 1-year life expectancy.
• Eastern Cooperative Group (ECOG) Performance Status score of 0 or 1.

• The laboratory test values should meet the following requirements:

  1. Absolute neutrophil count ≥ 1.5 x 109/L , Platelets ≥ 100 x 109/L ，hemoglobin ≥9g/dL
  2. Total bilirubin≤ 1.5 x institutional upper limit of normal,AST and ALT≤ 2.5 x institutional upper limit of normal
  3. Creatinine≤ 1.5 x institutional upper limit of normal ,if not, Creatinine Clearance ≥ 50 ml/min
  4. International normalized ratio (INR) and prothrombin time ≤1.5 x institutional upper limit of normal; and activated partial thromboplastin time (aPTT) ≤1.5 x institutional upper limit of normal
• Female patients must have a negative pregnancy test at baseline.

Exclusion Criteria:

• Patients who are participating in other clinical studies or are receiving other investigational drugs , or investigational devices within 4 weeks before the first dose of our study drugs. If patients are participating in non-interventional clinical trials, they can be included in this study.
• Patients who have a presence of unresectable or metastatic disease, the pathological diagnosis show the microscopically positive surgical margins or extranodal invasion, or residual disease of surgery，or had only segmentectomies or wedge resections.
• Patients with superior sulcus cancer.
• Patients who have received a surgery with total right lung resection.
• History of other malignancies within 5 years of the first dose of the study drug, except: malignant tumors that can be expected to recover after treatment.
• Prior treatment with other anti-cancer treatments or NSCLC including chemotherapy, radiotherapy, targeted therapy (such as small molecule tyrosine kinase inhibitors targeting EGFR, VEGFR or other pathways, monoclonal antibodies, etc.), immunotherapy, investigational therapy, etc. but except platinum based chemotherapy for adjuvant therapy.
• Major surgery within 3 weeks of the first dose of the study drug.
• Patients who have used traditional Chinese medicines and traditional Chinese medicine preparations with indications for anti-tumor therapy or adjuvant therapy for tumors within 14 days of the first dose of the study drug.
• Patients who have used the following drugs within 14 days before the first dose : strong inhibitors, strong inducers of CYP3A or CYP3A substrates with a narrow therapeutic index.
• Patients who have severe cardiovascular disease.
• Patients with a known allergy to Tartrazine，a dye used in 100mg capsules.
• Severe active infection, interstitial lung disease/pneumonitis, or any serious underlying disease that may interfere with the subject's treatment with the regimen within 2 weeks prior to the first dose of study drug.
• Active HIV virus antibody,Treponema pallidum antibody positive.
• Active hepatitis B, hepatitis C virus antibody positive, or active tuberculosis.
• Presence of active gastrointestinal (GI) disease or other conditions that will interfere significantly with the absorption, distribution, metabolism, or excretion of study drugs.
• According to the judgment of the investigator, other conditions may affect the compliance of the protocol or affect the subject's signing of the informed consent, or is not suitable for participating in this clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ensatinib; Ensatinib ( 225 mg, once daily), in accordance with the randomization schedule	Drug: Ensartinib; Ensartinib 225 mg once daily until disease recurrence or up to 2 years, whichever occurs earlier.; Other Names: X-396
Placebo Comparator: Placebo; Placebo ( 225 mg, once daily), in accordance with the randomization schedule	Drug: Placebo; Placebo 225 mg once daily until disease recurrence or up to 2 years, whichever occurs earlier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease free survival (DFS)	From date of randomization until date of tumor recurrence or death, whichever occurs earlier	up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
DFS rate at 3 years	Assessed at 3 years
DFS rate at 5 years	Assessed at 5 years
Overall survival (OS)	Assessed at 5 years
OS rate at 5 years	up to 5 years

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2022
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): July 23, 2025

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: August 21, 2024
• Last Verified: August 1, 2024

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Ensartinib
• Other Study ID Numbers: BTP-42338

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