QL1706 With Olaparib for Previously Treated HER2-negative Breast Cancer Patients With Homologous Recombination Deficiency (HRD)

Inclusion criteria

• Age 18 - 75 years; Eastern Cooperative Oncology Group (ECOG) score status 0-1.
• Pathologically documented HER2-negative locally advanced or metastatic breast cancer (IHC0, IHC 1+& IHC 2+/ISH-) that was hormone-receptor positive (i.e., estrogen-receptor positive, progesterone-receptor positive, or both) or was triple negative.
• Has been treated with 2-4 previous therapy regimens for metastatic disease.
• HRD positive confirmed, known germline and/or systemic BRCA mutation status that is predicted to be deleterious or suspected deleterious allow preferential enrolment.
• At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1.
• Has protocol-defined adequate bone marrow, renal, hepatic and blood clotting functions.
• A life expectancy of at least 12 weeks.
• Female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception or avoid intercourse during and upon completion of the study and after the last dose for at least 3 months. Negative serum or urine pregnancy test within 7 days before study enrollment, and must be a non-lactating subject.
• Volunteer to participate in this study and sign the informed consent.

Exclusion criteria

• Has any active autoimmune disease, which may worsen when receiving immune stimulants.
• Prior treatment with immune checkpoint inhibitors (ICI) (anti-CTLA-4, anti-PD-1, anti-PD-L1, combined therapy anti-PD-1/PD-L1 with anti-CTLA-4) or olaparib for advanced disease.
• Has unresolved toxicities from previous anticancer therapy.
• Has uncontrolled or significant cardiovascular disease.
• Discontinuation of prior anti-PD-1/PD-L1/CTLA-4 therapy due to immune-related toxicity.
• Known history or evidence of interstitial lung disease or active non-infectious pneumonitis.
• Has received a live vaccine vaccination within 28 days before enrolment.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known history of or is positive for Hepatitis B or Hepatitis C.
• Any severe or poorly controlled systemic disease such as poorly controlled hypertension, active bleeding susceptibility or active infection, as judged by the investigator.
• Has untreated or clinically active central nervous system metastases.
• Female subjects who are pregnant, lactating or plan to become pregnant during the study.
• Has any other condition that per protocol or in the opinion of the investigator is inappropriate for the study.