Second-Line Sacituzumab Tirumotecan Plus Anlotinib for Advanced Driver Gene-Negative Non-Squamous NSCLC

Prior treatment

• Prior treatment with TROP2-targeted therapy or any drug targeting topoisomerase I (including ADCs).
• Other malignancies within 3 years prior to dosing (except locally cured tumors like basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, etc.).
• Presence of major cardiovascular diseases or risk factors within 6 months prior to dosing (e.g., myocardial infarction, severe arrhythmias, active myocarditis, major vascular disease requiring surgery).
• Bleeding symptoms or any ≥CTCAE grade 3 bleeding event with unhealed wounds, ulcers, or fractures within 1 month prior to first dose.
• Major surgery within 4 weeks prior to dosing or planned major surgery during the study.
• Current use of strong CYP3A4 inducers (must be avoided at least 3 weeks prior).
• Live vaccine within 30 days prior to dosing or planned during the study.

Other illness

• Tumors histologically or cytologically confirmed with mixed small cell lung cancer, squamous cell carcinoma, neuroendocrine carcinoma, or carcinosarcoma components.
• Poorly controlled hypertension (systolic \> 160 mmHg and/or diastolic \> 100 mmHg).
• History of (non-infectious) interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroid treatment, or current active/suspected ILD/pneumonitis.
• Documented severe dry eye syndrome, severe meibomian gland disease and/or blepharitis, or corneal disease preventing/delaying healing.
• Active chronic inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess, or acute gastrointestinal bleeding.
• Risk of esophageal-tracheal or esophageal-pleural fistula.
• Tumors invading major blood vessels or high risk of fatal bleeding.
• Known active tuberculosis.
• History of allogeneic organ transplant or allogeneic hematopoietic stem cell transplant.
• HIV positive, history of AIDS, or active syphilis infection.
• Any condition that, in the investigator's opinion, interferes with the evaluation of the study drug or compromises subject safety.

Other

• Known meningeal, brainstem, spinal cord metastases and/or compression, or active central nervous system (CNS) metastases.
• Pregnant or lactating women.

• Age ≥18 years, regardless of gender.
• Histologically or cytologically confirmed locally advanced (Stage IIIB/IIIC) or metastatic (Stage IV) non-squamous NSCLC, progressing after prior anti-PD-1/L1 monoclonal antibody combined with platinum-based doublet chemotherapy.
• No known driver gene alterations such as EGFR, ALK, ROS1, NTRK, BRAF, MET, KRAS, HER2, RET, etc.
• At least one measurable target lesion not previously irradiated, assessed by the investigator per RECIST v1.1.
• ECOG performance status score of 0 or 1.
• Asymptomatic or locally treated and stable brain metastases are allowed.
• Life expectancy ≥ 12 weeks.
• Adequate organ and bone marrow function.
• Agreement to use effective medical contraception from signing informed consent until 6 months after the last dose.
• Voluntary participation, signed informed consent, and ability to comply with the protocol.