The Efficacy of TROP2-ADC in Advanced Extrapulmonary High-Grade Neuroendocrine Neoplasms Failure of Standard Therapy

Prior treatment

• (1) Active CNS metastases and/or carcinomatous meningitis.
  • Exception: Subjects with treated brain metastases may enroll if: Stable for ≥28 days prior to study initiation, Off steroids for brain metastases ≥28 days. Note: Carcinomatous meningitis excluded regardless of stability.
  • (2) Major surgery, open biopsy, or significant trauma within 28 days prior to first dose.
  • (3) History of severe interstitial lung disease (ILD) with inadequate control. (4) Uncontrolled hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg despite antihypertensive therapy).
  • (5) Poorly controlled cardiovascular disease, including:
  • NYHA Class II+ heart failure
  • Unstable angina
  • Myocardial infarction within 1 year
  • Clinically significant supraventricular/ventricular arrhythmias refractory to intervention (6) Clinically significant bleeding within 3 months prior to first dose (e.g., GI bleeding, hemorrhagic gastric ulcer, vasculitis). (7) Arterial/venous thromboembolic events within 6 months prior to first dose (e.g., CVA, TIA, cerebral hemorrhage, DVT, PE).Exception: Superficial thrombosis per investigator assessment.
  • (8) Active other malignancy requiring therapy. Exceptions: Non-melanoma skin cancer in situ with curative treatment.
  • (9)Pregnancy or lactation. (10)Other factors potentially leading to premature discontinuation per investigator judgment: Severe comorbidities (including psychiatric), Critical lab abnormalities, Social/familial factors compromising safety/data integrity (11)TROP2-targeted agents, ADC drugs (e.g., 8201)Topoisomerase I inhibitor-containing ADCs (12)Live vaccination within 30 days prior to first dose or planned during study.
  • (13)Requirement for strong CYP3A4 inhibitors/inducers within 2 weeks prior to first dose or during study.
  • (14) Palliative radiotherapy to known metastatic sites within 2 weeks prior to first dose.
  • (15)Systemic anti-infective therapy within 1 week prior to first dose. Severe ocular conditions including: (16)Dry eye syndrome, Meibomian gland dysfunction, Blepharitis, Corneal disease delaying healing (17)Other exclusionary conditions per investigator assessment.

• Provide written informed consent and voluntarily participate in the study.
• Aged 18-75 years, male or female.
• Histologically or cytologically confirmed diagnosis of one of the following:
  • Metastatic neuroendocrine carcinoma (NEC) Neuroendocrine tumor (NET) Grade 3 (G3) Mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) with \>30% neuroendocrine component.
• Progression after at least one prior line of systemic therapy.
• ECOG Performance Status of 0 or 1.
• Life expectancy ≥3 months.
• At least one measurable lesion per RECIST 1.1 at baseline:
• Lesions must not have received prior local therapy (e.g., radiotherapy). Lesions within prior radiotherapy fields are acceptable if progression is documented.
• Adequate organ function (no blood products/growth factors within 14 days prior):
  • Absolute neutrophil count (ANC) ≥1.5×10⁹/L
  • Platelets ≥100×10⁹/L ③Hemoglobin ≥8 g/dL ④Total bilirubin ≤1.5 × ULN ⑤ALT/AST ≤2.5 × ULN (≤5 × ULN if liver metastases present) ⑥Serum creatinine ≤1.5 × ULN or creatinine clearance \>60 mL/min (Cockcroft-Gault formula).
  • 9\. Contraception requirements:
  • Females of childbearing potential:
  • Negative serum pregnancy test within 72 hours prior to dosing. Use highly effective contraception (e.g., IUD, oral contraceptives, condoms) during and for ≥3 months after last dose.
  • Males with fertile partners:
  • Use effective contraception during and for ≥3 months after last dose.