Phase II Study of HLX43 Monotherapy or Combined With Immune Checkpoint Inhibitors in Patients With Locally Advanced, Recurrent, or Metastatic Triple-negative Breast Cancer.

Prior treatment

• Prior topoisomerase I-targeting therapy (e.g., irinotecan, topotecan, or ADCs).
• Prior grade ≥3 immune-related adverse event during immunotherapy.
• Active systemic infection requiring IV antibiotics within 2 weeks before randomization.
• Moderate or strong CYP2D6/CYP3A inhibitor or inducer use within 2 weeks before randomization.
• Systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressants within 2 weeks before randomization .
• Live or attenuated live vaccine within 4 weeks before randomization.
• Participation in another interventional trial within 30 days before consent .

Other illness

• Second primary malignancy within 2 years before randomization (except cured carcinoma in situ or stage I tumors).
• Uncontrolled, recurrent malignant pleural, pericardial, or ascitic effusions requiring repeated drainage.
• Clinically significant pulmonary impairment.
• Uncontrolled cardiovascular or cerebrovascular disease .
• Active or suspected autoimmune disease .
• Hypersensitivity to mAbs, large-molecule biologics, or drug formulation excipients.
• Active pulmonary tuberculosis.
• Active HBV , HCV , or HBV/HCV co-infection.
• Any condition posing unacceptable safety risk or interfering with study conduct per investigator judgment.

Other

• Active CNS metastases, spinal cord compression, or carcinomatous meningitis.
• Known immunodeficiency.
• Pregnancy or lactation.

• Voluntary written informed consent obtained before any study procedures.
• Age ≥ 18 years at consent; no gender restriction.
• Histopathologically confirmed TNBC: ER \< 1%, PR \< 1%, HER2 IHC 0/1+/2+ with no FISH amplification.
  • Phase I: Recurrent or metastatic TNBC after ≥1 prior line of standard systemic therapy.
  • Phase II: Unresectable locally advanced, recurrent, or metastatic TNBC with no prior systemic anti-cancer therapy for this stage (palliative radiotherapy to metastases allowed; neoadjuvant/adjuvant therapy permitted if completed ≥6 months before recurrence/metastasis).
• At least one RECIST v1.1-measurable lesion documented within 4 weeks before randomization.
  • Note: Target lesions must not be in irradiated fields or the CNS. If only measurable lesion is irradiated, imaging must confirm progression post-radiotherapy.
• Archival FFPE tumor tissue (≤6 months old, ≤2 years max) for PD-L1 testing; fresh biopsy acceptable if archival tissue is unavailable or inadequate.
  • Note: Specimens must be non-irradiated FFPE blocks/slides with pathology report confirming malignancy and adequacy.
• Washout: ≥3 weeks (or 5 half-lives, whichever is shorter) after major surgery, radiotherapy (except palliative bone RT), chemotherapy, targeted therapy, or immunotherapy; ≥1 week after minor surgery or anti-tumor TCM. All treatment-related AEs resolved to CTCAE v6.0 Grade ≤1 (stable Grade 2 peripheral neuropathy and alopecia exempted).
• ECOG PS 0-1, assessed ≤7 days before randomization.
• Life expectancy \>3 months.
• Adequate hematologic, hepatic, and renal function per labs ≤7 days before randomization.