A Study of SYS6043 Versus Investigator's Choice Chemotherapy as First-Line Treatment in Patients With Unresectable Locally Recurrent or Metastatic Triple-Negative Breast Cancer

Prior treatment

• Diagnosis of another malignancy within 3 years prior to randomization.
• Presence of cardiovascular and cerebrovascular diseases or cardiovascular cerebrovascular risk factors.
  • 4 History of non infectious interstitial lung disease (ILD) or non infectious pneumonitis requiring steroid therapy.
  • 5 Clinically significant pulmonary impairment secondary to underlying pulmonary disease.
  • 6 Tumor invasion into adjacent vital organs and blood vessels. 7 Severe infection occurring within 4 weeks prior to randomization. 8 History of esophageal and gastric varices, severe ulcer, gastrointestinal perforation, gastrointestinal obstruction, intra abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to randomization.
  • 9 Active or well documented prior history of inflammatory bowel disease. 10 Uncontrolled systemic disease as judged by the investigator. 11 Participants with active viral hepatitis; positive hepatitis C virus (HCV) with HCV RNA above the lower limit of quantification of the assay.
  • 12 Positive human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection.
  • 13 Known hypersensitivity to active pharmaceutical ingredients or excipients of study drug.
  • 14 Known history of allogeneic solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
  • 15 Pregnant or breastfeeding women. 16 Prior receipt of B7 H3 targeted therapy; prior irinotecan, topotecan, or any chemotherapy agents targeting topoisomerase I (including ADCs).
  • 17 Prior treatment with the same agent as the investigator selected chemotherapy.
  • 18 Live vaccine administered within 4 weeks before randomization, or planned administration of live vaccine during study treatment.
  • 19 Insufficient washout period for prior anti tumor therapy before the first dose of study drug.
  • 20 Chronic concomitant use of systemic corticosteroids or other immunosuppressive agents.
  • 21 Local or systemic disease unrelated to malignancy, or diseases/symptoms secondary to tumor.
  • 22 Any condition that, in the investigator's opinion, would interfere with the evaluation of study drug, participant safety, or interpretation of study results, or any other condition rendering the participant unsuitable for study participation as assessed by the investigator.
  • 23 Systemic administration of strong CYP3A4 / CYP2C8 inhibitors or strong inducers, or OATP1B1 / OATP1B3 inhibitors within 14 days prior to the first dose of study drug, or requiring continued systemic use of such agents during study treatment.

Other

• Presence of spinal cord compression, clinically active brain metastase.

• Age ≥ 18 and ≤ 75 years at the time of signing the informed consent form, with no restriction on sex.
• Histologically and/or cytologically confirmed triple negative breast cancer (TNBC) meeting both of the following criteria: a) Human epidermal growth factor receptor 2 (HER2) negative; b) Estrogen receptor (ER) negative and progesterone receptor (PR) negative.
• De novo metastatic disease, or unresectable recurrent and/or metastatic disease occurring after completion of curative intent therapy.
• No prior systemic anti tumor therapy for unresectable recurrent or metastatic disease.
• PD L1 expression determined by the sponsor designated central laboratory using tumor tissue collected at screening. Participants must meet either: a) PD L1 negative expression (CPS \< 10); OR b) PD L1 positive expression (CPS ≥ 10).
• At least one measurable lesion per RECIST version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Expected survival of at least 12 weeks.
• Deemed by the investigator to be suitable for one of the investigator's choice chemotherapy regimens (paclitaxel, nab paclitaxel, capecitabine, eribulin, or carboplatin).
• Adequate organ and bone marrow function (no transfusion, recombinant human thrombopoietin, or colony stimulating factor within 2 weeks prior to randomization).
• Participants must have recovered from all toxicities attributable to prior therapies (recovered to Grade ≤ 1 per CTCAE Version 6.0, or otherwise meeting protocol specified entry criteria).
• Serum pregnancy test negative within 7 days prior to randomization for women of child bearing potential.
• Voluntarily agrees to participate in this study, provides signed informed consent, and is able to comply with protocol required visits and procedures.