This study is an open-label, randomized, multicenter phase II/III clinical trial designed to evaluate the efficacy, safety, and tolerability of Andamertinib with or without platinum-based chemothsrapy versus platinum-based chemotherapy in previously untreated participants with locally advanced or metastatic non-squamous NSCLC harboring EGFR atypical mutations. The study comprises two stages: phase II (dose-exploration stage) and phase III (pivotal study stage)

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:

1. Age ≥18 years at the time of ICF signing.
2. Histologically or cytologically confirmed, unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) non-squamous non-small cell lung cancer (NSCLC).
3. Confirmed EGFR atypical mutation.
4. No prior systemic therapy for locally advanced or metastatic NSCLC.
5. At least one measurable lesion as defined by RECIST v1.1.
6. ECOG PS ≤1.
7. Life expectancy≥12 weeks.
8. Adequate organ function confirmed within 7 days prior to the first dose of study treatment
9. 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.
10. Non-sterilized males: Abstinence or contraception use; No sperm donation.
11. 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:

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