A Phase II Study of AK146D1 Combined With AK112 in Advanced Breast Cancer

Inclusion criteria

• Be able to understand and voluntarily sign the written informed consent form.
• Aged of ≥ 18 years and ≤75 years.
• ECOG PS 0 or 1.
• The expected lifespan is ≥3 months.
• Patients with histologically confirmed locally advanced, recurrent, or metastatic breast cancer who are not eligible for curative surgical resection; and who have histologically or cytologically confirmed HER2-negative disease.
• At least one measurable lesion according to RECIST v1.1. Patients with only bone lesions or cutaneous lesions are not ineligible for enrollment.
• Have sufficient organ function.
• Females patients must not be pregnant at screening or have evidence of non-childbearing potential. Agree to use medically accepted methods of contraception.

Exclusion criteria

• Patients had breast cancer amenable to curative treatment at study enrollment.
• Concurrent other histopathological types confirmed by tumor histology or cytology.
• Having other active malignancies within 3 years.
• Currently participating in another interventional clinical study.
• Presence of active metastases to the central nervous system. For patients with asymptomatic brain metastasis or stable symptoms after treatment can be included.
• Prior treatment with any therapy targeting Trop-2 or Nectin-4, or any chemotherapy agent targeting topoisomerase I.
• Receipt of systemic anti-tumor therapy (including chemotherapy, immunotherapy, biological agents, etc.) within 4 weeks prior to the first dose.
• Toxicity of previous antineoplastic therapy has not resolved to NCI CTCAE 6.0 grade 1 or lower.
• Patients with clinically significant cardiovascular or cerebrovascular diseases or risks.
• Patients with active autoimmune diseases requiring systemic treatment within 2 years.
• Receipt of systemic anti-infective therapy within 2 weeks prior to the first dose.
• Known to be positive for HIV and other infections.
• Previous history of severe hypersensitivity reactions.
• Live attenuated vaccines were received within 4 weeks.
• Patients with a history of mental illness and incapacitated or limited capacity.
• Any disease or condition that, in the opinion of the investigator, would compromise patient safety or interfere with study assessments.