Inclusion Criteria:
* Histologically or cytologically confirmed non-squamous NSCLC that is locally advanced (Stage ⅢB/ⅢC) or metastatic (Stage Ⅳ) and not amenable to curative surgery and/or curative concurrent/sequential chemoradiotherapy \[according to the 8th edition TNM staging system for lung cancer by the Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC)\], with tissue or blood-based genetic testing showing EGFR-sensitive mutations (19del and L858R).
* Subjects must have received prior EGFR-TKI therapy for locally advanced or metastatic disease and experienced treatment failure (documented radiographic disease progression), and must meet one of the following requirements: a) progressed after first- or second-generation EGFR-TKI, and histologically confirmed T790M-negative after treatment failure; b) progressed after third-generation EGFR-TKI regardless of T790M mutation status; and progressed after platinum-based chemotherapy or have chemotherapy intolerance.
Note: For subjects who have received neoadjuvant or adjuvant EGFR-TKI therapy, if disease progression occurs ≤12 months from the last dose, this EGFR-TKI is considered first-line therapy for locally advanced or metastatic disease.
* Male or female subjects aged ≥18 years and ≤75 years who have signed the informed consent form.
* ECOG performance status of 0 or 1, with an expected survival \>6 months.
* Agree to provide previously stored tumor tissue specimens or undergo biopsy to collect tumor lesion tissue for biomarker analysis.
* Adequate organ function: Laboratory tests must meet the following requirements: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin ≥90 g/L, white blood cell count ≥3.0×10\^9/L; Liver function: Total bilirubin \<1.5× upper limit of normal (ULN), aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), and alkaline phosphatase (ALP) ≤2.5×ULN; If liver metastases are present, AST and ALT ≤5.0×ULN; If liver and/or bone metastases are present, ALP ≤5.0×ULN. Renal function: Serum creatinine (Scr) ≤1.5×ULN; Urine routine test shows urine protein \<2(+); If baseline urine protein ≥2(+), 24-hour urine protein quantification must be ≤1.0 g; Coagulation function: International normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5×ULN.
Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%.
-Able to communicate effectively with the investigator and comply with study requirements for visits, treatment, laboratory tests, and other relevant regulations.
Exclusion Criteria:
* Squamous cell carcinoma (including adenosquamous carcinoma and undifferentiated carcinoma); small cell lung cancer (including combined small cell and non-small cell lung cancer); patients who have previously received systemic therapy (prior adjuvant or neoadjuvant therapy is permitted).
* Patients with symptomatic brain metastases at the start of treatment (patients with previously treated brain metastases are eligible if asymptomatic brain metastases persist for at least 4 weeks while on stable dose medication).
* Patients who participated in an interventional oncology clinical trial concurrently during first-line therapy or within 30 days prior to first-line therapy.
* History of tracheoesophageal fistula, gastrointestinal perforation or fistula, or intra-abdominal abscess within 6 months before treatment initiation.
* Patients with severe cardiovascular or cerebrovascular diseases, including cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction within 6 months before enrollment, and significant vascular disease (including but not limited to aortic aneurysm requiring surgical repair or recent arterial thrombosis); patients with unstable angina, New York Heart Association (NYHA) class ≥II heart failure; mean resting corrected QT interval (QTc) \>470 ms; any clinically significant resting ECG rhythm, conduction, or morphological abnormalities, such as complete left bundle branch block, third-degree heart block, second-degree heart block, interval \>250 ms. Any factors increasing the risk of QTc prolongation or arrhythmic events, such as heart failure, electrolyte abnormalities (including: serum/plasma potassium \< LLN; serum/plasma magnesium \< LLN; serum/plasma calcium \< LLN), congenital long QT syndrome, family history of long QT syndrome, or sudden unexplained death in a first-degree relative under 40 years of age, or any concomitant medication known to prolong QT interval and cause torsades de pointes.
* Uncontrolled systemic diseases as determined by the investigator:
1. Poorly controlled diabetes (fasting blood glucose ≥10 mmol/L on two consecutive occasions);
2. Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg);
3. Presence of symptomatic pleural effusion, pericardial effusion, or ascites requiring repeated drainage (\>1 time/week).
* History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, current ILD or non-infectious pneumonitis, or suspected ILD or non-infectious pneumonitis at screening that cannot be ruled out by imaging examination.
* Clinically significant pulmonary impairment due to concurrent lung disease, including but not limited to any underlying pulmonary disease (such as pulmonary embolism within 3 months before first dosing, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) or any autoimmune, connective tissue, or inflammatory disease that may involve the lungs (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
* Subjects with active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, intra-abdominal abscess, or acute gastrointestinal bleeding.
* Tumor invasion of surrounding vital organs and vessels (such as heart, esophagus, superior vena cava, etc.) or risk of developing tracheoesophageal fistula or esophagopleural fistula.
* Toxicities from prior anti-tumor therapy that have not recovered to ≤Grade 1 (based on NCI CTCAE version 5.0 assessment) or to the level specified in inclusion/exclusion criteria (except for alopecia, fatigue, and other toxicities that the investigator deems pose no safety risk).
* Known or suspected hypersensitivity to furmonertinib and sacituzumab tirumotecan and/or other components of their formulations.
* Women of childbearing potential or male subjects who are unwilling to use effective contraception during the study or for 6 months after the last dose of study drug.
* Active hepatitis B (positive hepatitis B surface antigen (HBsAg) requiring HBV-DNA testing; HBV-DNA ≥500 IU/mL or higher than the lower limit of detection, whichever is higher) or hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the lower limit of detection).
* Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
* Other conditions that the investigator considers unsuitable for enrollment in addition to the above situations.
