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

Официальное название

A Phase II Study to Evaluate the Efficacy and Safety of HLX43 (an Anti-PD-L1 ADC) as a Monotherapy or in Combination With Immune Checkpoint Inhibitors in Subjects With Locally Advanced, Recurrent or Metastatic Triple-negative Breast Cancer (TNBC).

Обзор

The study is being conducted to explore the reasonable dosage and evaluate the efficacy, safety and tolerability of HLX43 (Anti-PD-L1 ADC) as a monotherapy or in combination with immune checkpoint inhibitors in Subjects with locally advanced, recurrent or metastatic triple-negative breast cancer (TNBC).

Вмешательства

• Препарат HLX43 DOSE 1 IN ≥2L TNBC
  Dose 1; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
• Препарат HLX43 DOSE 2 IN ≥2L TNBC
  Dose 2; HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
• Препарат HLX43 DOSE 1 + HLX10
  HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8. HLX10 is a humanized anti-PD-1 monoclonal antibody that functions as an immune checkpoint inhibitor.
• Препарат HLX43 DOSE1 IN 1L TNBC
  HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
• Препарат HLX43 DOSE 2 IN 1L TNBC
  HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8.
• Препарат HLX43 DOSE2 + HLX10
  HLX43 is an anti-PD-L1 monoclonal antibody conjugated with a novel high potency DNA topoisomerase I (topo I) inhibitor, with a drug-antibody-ratio (DAR) of 8. HLX10 is a humanized anti-PD-1 monoclonal antibody that functions as an immune checkpoint inhibitor.

Первичные конечные точки

• ORR [Срок оценки: up to 24 weeks]
• PFS [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• Prior topoisomerase I-targeting therapy (e.g., irinotecan, topotecan, or ADCs).
• Second primary malignancy within 2 years before randomization (except cured carcinoma in situ or stage I tumors).
• Prior grade ≥3 immune-related adverse event during immunotherapy.
• Uncontrolled, recurrent malignant pleural, pericardial, or ascitic effusions requiring repeated drainage.
• Active CNS metastases, spinal cord compression, or carcinomatous meningitis.
• Clinically significant pulmonary impairment.
• Uncontrolled cardiovascular or cerebrovascular disease .
• 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 .
• Active or suspected autoimmune disease .
• Live or attenuated live vaccine within 4 weeks before randomization.
• Hypersensitivity to mAbs, large-molecule biologics, or drug formulation excipients.
• Active pulmonary tuberculosis.
• Known immunodeficiency.
• Active HBV , HCV , or HBV/HCV co-infection.
• Pregnancy or lactation.
• Participation in another interventional trial within 30 days before consent .
• Any condition posing unacceptable safety risk or interfering with study conduct per investigator judgment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Harbin Medical University Affiliated Cancer Hospital — Харбин

Идентификаторы

NCT: NCT07487519 · HLX43-BC202

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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