Andamertinib With or Without Platinum-doublet Chemotherapy Versus Platinum-doublet Chemotherapy in Patients With NSCLC Harboring Atypical EGFR Mutations

This a three-stage study consist a Screening Phase (Day -28 to -1), a Treatment Phase (until treatment discontinuation), and a Follow-up Phase (including end of treatment visit (EOT),end of study visit(EOS), safety follow-up and survival follow-up).

Inclusion criteria

• Age ≥18 years at the time of ICF signing.
• Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC).
• Confirmed EGFR atypical mutation.
• No prior systemic therapy for locally advanced or metastatic NSCLC.
• At least one measurable lesion as defined by RECIST v1.1.
• ECOG PS ≤1.
• Life expectancy≥12 weeks.
• Adequate organ function confirmed within 7 days prior to the first dose of study treatment
• Female participants must use adequate contraceptive measures during study participation and for 90 days after the last dose of study treatment and must not be breastfeeding; female subjects not of childbearing potential must meet at least one of the following criteria at screening: Postmenopausal status; Documentation of irreversible surgical sterilization.
• Non-sterilized males: Abstinence or contraception use; No sperm donation.
• Willing and able to provide signed ICF and to comply with all requirements and restrictions listed in the ICF and this study protocol.

Exclusion criteria

• Presence of specific genetic alterations for which approved targeted therapies are available.
• Recent participation (within 28 days) in another interventional clinical trial.
• Major surgery within 28 days prior to study entry or planned during the study period.
• Recent use of anti-tumor traditional proprietary medicine or local anti-tumor therapy.
• Need for specific concomitant medications (e.g., metformin) that cannot be paused during the study.
• History of another active malignancy within the past 5 years (except for specific cured cancers).
• Toxicities from prior therapy have not recovered to acceptable levels.
• Presence of symptomatic or uncontrolled brain metastases, carcinomatous meningitis, or spinal cord compression.
• Symptomatic and uncontrolled third-space fluid accumulations (e.g., pleural effusion, ascites).
• Severe cardiovascular/cerebrovascular disease or risk factors (e.g., heart failure, history of myocardial infarction, QT prolongation, uncontrolled hypertension, etc.).
• History or presence of interstitial lung disease, or drug/radiation-related pneumonitis.
• Active autoimmune or inflammatory diseases.
• Active, uncontrolled infection (including HBV, HCV, HIV, syphilis, tuberculosis, etc.).
• Gastrointestinal disorders or surgery affecting drug ingestion or absorption.
• Active keratitis or ulcerative keratitis.
• History of hypersensitivity to the study drug, its analogs, or chemotherapy drugs (pemetrexed/platinum agents).
• Recent administration (within 30 days) of a live attenuated vaccine.
• Psychiatric disorders or substance abuse potentially affecting compliance.
• Any other condition deemed by the investigator as unsuitable for study participation.