Comparative ¹⁸F-FDG and ⁶⁸Ga-MY6349 PET/CT Imaging for Assessing TROP2 ADC Therapeutic Efficacy in EGFR-TKI Resistant Advanced NSCLC

Inclusion Criteria: * Aged ≥18 years at the time of signing the informed consent form, with no restriction on gender. * Histologically or cytologically confirmed non-squamous non-small cell lung cancer (NSCLC), classified as locally advanced Stage IIIB/IIIC or metastatic Stage IV NSCLC (per the 8th edition of UICC/AJCC TNM staging system for lung cancer), and not eligible for curative resection and/or definitive radiotherapy (with or without concurrent chemotherapy). * Presence of EGFR sensitizing mutations (exon 19 deletion or exon 21 L858R point mutation). * Subjects who have received first-line third-generation EGFR-TKI therapy with documented treatment failure. For subjects previously treated with third-generation EGFR-TKIs in adjuvant, neoadjuvant or consolidation settings, such TKI therapy will be regarded as first-line treatment for locally advanced or metastatic disease if disease progression occurs within ≤6 months after the last dose. * At least one measurable lesion as defined by RECIST v1.1; previously irradiated lesions shall not be selected as target lesions. Subjects with only cutaneous or osseous lesions are not eligible for enrollment. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to study drug administration. * Estimated life expectancy ≥12 weeks. * Adequate organ and bone marrow function (no blood transfusion, recombinant thrombopoietin or colony-stimulating factor administered within 2 weeks before dosing), defined as follows: 1. Hematology: Absolute neutrophil count (NEUT#) ≥1.5×10⁹/L; platelets (PLT) ≥100×10⁹/L; hemoglobin ≥90 g/L. 2. Hepatic function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN; albumin ≥30 g/L. For subjects with hepatic metastases at baseline, ALT and AST ≤5×ULN, TBIL ≤3×ULN. 3. Renal function: Creatinine clearance ≥50 mL/min (calculated using the standard Cockcroft-Gault formula). 4. Coagulation function: International normalized ratio (INR), activated partial thromboplastin time (APTT) and prothrombin time (PT) ≤1.5×ULN. * Females of childbearing potential and male subjects whose partners are of childbearing potential must agree to use effective medical contraception from the date of informed consent signature through 6 months after the last study drug administration. * The subject voluntarily participates in this study, signs the informed consent form, and is able to comply with all protocol-specified visits and relevant procedures. Exclusion Criteria: * Tumor histology or cytology confirms mixed components including small cell lung cancer, neuroendocrine carcinoma, carcinosarcoma, or squamous cell carcinoma. * Subjects with known leptomeningeal metastases, brainstem metastases, spinal cord metastases/compression, or symptomatic unstable central nervous system (CNS) metastases are excluded unless they are off steroid therapy and maintain stable neurological status for at least two weeks after completion of definitive radiotherapy and steroid tapering. * Prior systemic anti-tumor therapy for locally advanced or metastatic non-squamous NSCLC other than third-generation EGFR-TKIs (e.g., chemotherapy, immunotherapy). * Previous treatment with any TROP2-targeted agents or therapeutics containing topoisomerase I inhibitors, including antibody-drug conjugates (ADCs), whether administered in adjuvant, neoadjuvant, or metastatic disease settings. * Thoracic radiotherapy with a cumulative dose \>30 Gy delivered within 6 months prior to the first dose; non-thoracic or extended-field radiotherapy with a cumulative dose \>30 Gy administered within 4 weeks prior to the first dose. Palliative radiotherapy for symptom control is permitted only if completed at least 2 weeks before study drug initiation. * History of another primary malignant tumor within 3 years before the first dose, excluding malignancies cured by local therapy such as basal cell carcinoma of the skin, cutaneous squamous cell carcinoma, and cervical carcinoma in situ. * Presence of any of the following cardiovascular or cerebrovascular diseases or risk factors: 1. Myocardial infarction, unstable angina, acute or persistent myocardial ischemia, New York Heart Association (NYHA) Class III/IV heart failure, symptomatic or poorly controlled severe arrhythmia, cerebrovascular accident, transient ischemic attack, or other severe cardiovascular/cerebrovascular events within 6 months before dosing. 2. Medical history of myocarditis, primary cardiomyopathy, or specific cardiomyopathies. 3. Deep vein thrombosis, peripheral arterial thromboembolism, pulmonary embolism, or other severe thromboembolic events within 3 months prior to dosing (subjects may be enrolled if stably treated with low-molecular-weight heparin or equivalent anticoagulants for ≥2 weeks). 4. Life-threatening major vascular diseases including aortic aneurysm or aortic dissection requiring surgical intervention within 6 months before dosing. 5. Corrected QT interval (QTcF) \>470 ms. * Uncontrolled systemic diseases as judged by the investigator: 1. Poorly controlled diabetes mellitus (two consecutive fasting blood glucose readings ≥10 mmol/L). 2. Uncontrolled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg). 3. Clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once per week. * History of steroid-dependent non-infectious interstitial lung disease (ILD) or non-infectious pneumonitis; active ILD or non-infectious pneumonitis at screening; or suspicious ILD/pneumonitis that cannot be ruled out by screening imaging. * Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or history of severe corneal disorders that hinder or delay corneal wound healing. * Clinically significant severe pulmonary impairment secondary to concurrent lung disorders, including but not limited to underlying lung diseases (e.g., severe asthma, advanced chronic obstructive pulmonary disease, restrictive lung disease within 3 months prior to dosing); autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.); or prior pneumonectomy. * Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulceration, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal hemorrhage. * Active gastrointestinal disorders or other conditions that substantially alter the absorption, distribution, metabolism, or excretion of oral study drugs (e.g., refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow oral medication, history of extensive intestinal resection). * Risk of esophagotracheal or esophagopleural fistula; tumor invasion or compression of vital adjacent organs and vessels (heart, esophagus, superior vena cava, etc.) accompanied by relevant clinical manifestations such as superior vena cava syndrome. * Toxicities from prior anti-tumor therapy that have not resolved to Grade ≤1 per NCI CTCAE v5.0 or the thresholds specified in eligibility criteria (alopecia, fatigue, and other toxicities judged low-risk by the investigator are exempted). * Severe infection occurring within 4 weeks before dosing, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic antimicrobial therapy within 2 weeks before dosing. * Confirmed active pulmonary tuberculosis. Subjects with suspected active tuberculosis must undergo clinical examinations to rule out infection before enrollment. * Active hepatitis B (HBsAg-positive with HBV-DNA ≥500 IU/mL or above the lower limit of quantification, whichever is higher); active hepatitis C (anti-HCV positive with HCV-RNA above the lower limit of quantification); or concurrent HBV and HCV co-infection. * Positive human immunodeficiency virus (HIV) serology or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection. * History of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation. * Major surgery performed within 4 weeks prior to dosing or major surgery planned during study participation. * Known hypersensitivity to the study drug or any of its excipients (including polysorbate 20); history of severe hypersensitivity reactions to other biologic agents. * Non-specific immunomodulatory therapy (including but not limited to interferon, IL-2) or proprietary Chinese medicines with approved anti-tumor indications administered within 2 weeks before dosing. * Current use (or inability to discontinue prior to the first study dose) of drugs or herbal supplements that are strong cytochrome P450 (CYP) 3A4 inducers, with a minimum 3-week washout period required. All subjects shall avoid concomitant use of any CYP3A4-inducing medications, herbal supplements, and/or relevant foods throughout the study. * Live vaccine administered within 30 days before dosing or planned live vaccination during study participation. * Rapid clinical deterioration during screening, such as marked decline in performance status. * Pregnant or breastfeeding women. * Local or systemic non-malignant diseases, or tumor-induced diseases/symptoms that carry high medical risks and/or cause uncertainty in survival assessment, such as leukemoid reaction, cachexia, etc. * Any medical condition that, in the investigator's opinion, may confound the evaluation of the study drug, compromise subject safety, interfere with the interpretation of study results, or render the subject unsuitable for trial participation.