MDT-bridged Radical Therapy After Aumolertinib Introduction and Followed by MRD-guided Maintained Therapy for EGFR-mutated Unresectable Stage III NSCLC (APPROACH/CTONG2101)

NCT04841811 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: CTONG2101
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center, randomized, phase III study. It is aimed to firstly evaluate the effectiveness and safety of almonertinib induction therapy in EGFR-mutated patients with unresectable stage III non-small cell lung cancer, and to evaluate the effectiveness and safety of dynamic MRD guided maintenance therapy with almonertinib after induction therapy with almonertinib and local therapy (radical surgery or radiotherapy) evaluated by MDT diagnostic model. The study includes a screening period (not more than 28 days after the subject with signed informed consent before first medication), treatment period (including induction therapy with almonertinib\\ radical therapy under MDT model\\ consolidation therapy with almonertinib) and follow-up period.

Conditions

Lung Cancer

Keywords

EGFR; NSCLC; ctDNA; MDT

Outcome Measures

Primary Outcomes (2)

• Assess the anti-tumor activity by IRC: ORR

  The objective response rate (ORR) was assessed by IRC for all eligible subjects after 8 weeks of Almonertinib induction therapy. Until the disease progresses or in the absence of disease progression, the last evaluable data will be recorded in the ORR assessment. However, any CR or PR that occurs after the termination of the study treatment and receiving further anti-tumor therapy will not be included in the ORR calculation.

  8 weeks

• Assess the anti-tumor activity by IRC: Event free survival (EFS) rate

  The 18 months event-free survival period is defined as the time from random to the occurrence of any of the following events within 18 months, whichever occurs first: Tumor progression assessed by IRC according to RECIST 1.1; Tumor recurrence confirmed by IRC, including local recurrence or distant metastasis; Death caused by any cause.

  18 months

Secondary Outcomes (7)

• Assess the anti-tumor activity by investigators: ORR

  8 weeks

• Assess the anti-tumor activity by investigators: Event free survival (EFS)

  18 months

• Event free survival (EFS)

  2 years

• Overall survival (OS)

  more than 2 years

• Major pathological response (MPR)

  8 weeks

Study Arms (2)

Group A (almonertinib continuous treatment)

ACTIVE COMPARATOR

Subjects will be randomly assigned to groups A and B after radical therapy (surgery or radiothrapy) and will receive 110 mg of almonertinib once a day for 2 years or until disease recurrence or metastasis.

Drug: Almonertinib

Group B (ctDNA monitoring guided the almonertinib treatment)

EXPERIMENTAL

Subjects will be randomly assigned to group B after radical therapy (surgery or radiothrapy) and will receive almonertinib guided by ctDNA dynamic monitoring (every 3 months test ctDNA once, if it is positive, continue to receive almonertinib 110 mg once a day, if it is negative, stop almonertinib until ctDNA turns positive and receive almonertinib treatment again).

Drug: Almonertinib

Interventions

Almonertinib DRUG

ctDNA dynamic monitoring guided the Almonertinib treatment group after redical surgery orradiotherapy

Also known as: ctDNA dynamic monitoring guided the Almonertinib treatment

Group A (almonertinib continuous treatment); Group B (ctDNA monitoring guided the almonertinib treatment)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Over 18 years old (including 18 years old) and under 70 years old (including 70 years old).
• The Eastern Cooperative Oncology Group (ECOG) physical status score is 0 or 1, and there is no deterioration within 2 weeks before the study drug treatment, and the expected survival period is not less than 12 weeks.
• Stage III non-squamous cell non-small cell lung cancer confirmed by histopathology or cytology and determined by the investigator to be unresectable (International Association for the Study of Lung Cancer Eighth Edition Lung Cancer Staging).
• Tumor tissue samples or blood samples, pleural effusions, ascites effusions, and pericardial effusions are confirmed to be EGFR sensitive mutations (ie, exon 19 deletion or L858R, alone or coexisting, Or with other EGFR mutations, but patients with EGFR20 exon insertion mutations cannot be included in the group) by laboratory tests approved by the investigator.
• According to the RECIST1.1 standard, the subject must have at least one imaging measurable lesion. The baseline tumor imaging evaluation was performed within 28 days before the first medication.
• Women of childbearing age should take appropriate contraceptive measures from screening to 3 months after stopping the study treatment and should not breastfeed. Before starting the administration, the pregnancy test is negative, or meeting one of the following criteria proves that there is no risk of pregnancy:
• Postmenopausal is defined as age greater than 50 years，and amenorrhea for at least 12 months after stopping all exogenous hormone replacement therapy.
• For women younger than 50 years old, if the amenorrhea is 12 months or more after stopping all exogenous hormone treatments, and the luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels are within the laboratory postmenopausal reference value range, also It can be considered postmenopausal.
• Have received irreversible sterilization, including hysterectomy, bilateral ovariectomy or bilateral fallopian tube resection, except for bilateral fallopian tube ligation.
• Male subjects should use barrier contraception (ie, condoms) from screening to 3 months after the study treatment is stopped.
• The subjects themselves participated voluntarily and signed a written informed consent form.

You may not qualify if:

• Subjects who meet any of the following criteria cannot be included in this study:
• Have received any of the following treatments:
• Have received lung surgery in the past;
• Have used any EGFR tyrosine kinase inhibitor in the past;
• Previously received any systemic chemotherapy or immunotherapy for lung cancer;
• Receive any lung cancer radiotherapy in the past;
• The patient has undergone open surgery on other parts except the lungs within 14 days before using the study drug for ≤14 days.
• In addition to NSCLC, another malignant disease has been diagnosed in the past 5 years (excluding completely resected basal cell carcinoma, bladder carcinoma in situ, and cervical carcinoma in situ).
• Have used proprietary Chinese medicines with anti-tumor effects in the past. Those who have used proprietary Chinese medicines with anti-tumor effects but have been used for no more than 7 days and have been stopped for 2 weeks or more before the drug treatment in this study can be included in the group.
• There are serious or uncontrollable systemic diseases (such as severe mental, neurological, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, liver or kidney disease, left ventricular ejection fraction (LVEF) \< 50%, uncontrolled hypertension \[that is, it is still greater than or equal to CTCAE level 3 hypertension after drug treatment\]); suffering from swallowing dysfunction, active gastrointestinal disease, or other significant effects on the absorption of oral drugs, Disorders of distribution, metabolism, and excretion. Those who have had most gastrectomy operations in the past.
• Fever and body temperature above 38℃ in the past week, or active infection with clinical significance. Active tuberculosis. Active fungal, bacterial and/or viral infections requiring systemic treatment.
• Those who have active bleeding, new thrombotic diseases, are taking anticoagulant drugs, or have bleeding tendency;
• The resting electrocardiogram has major clinically significant abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, heart block above Ⅱ degree, clinically significant ventricular arrhythmia or atrial fibrillation, Unstable angina pectoris, congestive heart failure, chronic heart failure grade ≥ 2 by the New York Heart Association (NYHA).
• Myocardial infarction, coronary artery/peripheral artery bypass or cerebrovascular accident occurred within 3 months.
• The QT interval (QTc) of 12-lead ECG is ≥450 ms for males and ≥470 ms for females.

Sponsors & Collaborators

• Guangdong Association of Clinical Trials: lead
• Jiangsu Hansoh Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Guangdong Lung cancer institute

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Q. Zhou

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Y. Pan

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• X-N. Yang

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• A-W. Liu

  Second Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

• W-N. Feng

  First People's Hospital of Foshan

  PRINCIPAL INVESTIGATOR

• L-H. Sun

  The First Affiliated Hospital of Nanchang University

  PRINCIPAL INVESTIGATOR

• T-M. Zhang

  Beijing Chest Hospital, Capital Medical University

  PRINCIPAL INVESTIGATOR

• X-R. Dong

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• M-F. Zhao

  First Hospital of China Medical University

  PRINCIPAL INVESTIGATOR

• H. Zhang

  The Affiliated Hospital of Xuzhou Medical University

  PRINCIPAL INVESTIGATOR

• Y. Fan

  Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute)

  PRINCIPAL INVESTIGATOR

• Y. Yang

  The Third People's Hospital of Chengdu

  PRINCIPAL INVESTIGATOR

• P-L. Wang

  Zhejiang University

  PRINCIPAL INVESTIGATOR

• Q-W. Meng

  The Affiliated Cancer Hospital of Harbin Medical University,

  PRINCIPAL INVESTIGATOR

• R-R. Zhou

  The Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

• Y-S. Shu

  Northern Jiangsu People's Hospital

  PRINCIPAL INVESTIGATOR

• B-H. Wang

  Northern Jiangsu People's Hospital

  PRINCIPAL INVESTIGATOR

• H-P. Xu

  Fujian Cancer Hospital

  PRINCIPAL INVESTIGATOR

• J. Li

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

• H. Luo

  Cancer Hospital of Jiangxi Province

  PRINCIPAL INVESTIGATOR

• Q. Bu

  First Affiliated Hospital of Guangxi Medical University

  PRINCIPAL INVESTIGATOR

• H-J. Wang

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• K. Zhao

  Wuhan Central Hospital

  PRINCIPAL INVESTIGATOR

• J. Zhao

  Peking University Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

• W-R. Yao

  Jiangxi Provincial People's Hopital

  PRINCIPAL INVESTIGATOR

• J-H. Lai

  Fujian Medical University Union Hospital

  PRINCIPAL INVESTIGATOR

• S-Y Maggie. Liu

  Guangdong Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

• Q-T. Yu

  Affiliated Cancer Hospital & Institute of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

• W-H. Zhao

  Affiliated Cancer Hospital & Institute of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 12, 2021
• Study Start: June 20, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)