A Randomised, Open-label, Multicentre Phase III Clinical Study to Evaluate the Efficacy and Safety of JS105 Combined With Dalpiciclib and Fulvestrant Compared With Dalpiciclib and Fulvestrant in Patients With PIK3CA-mutated, HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer.

A Randomised, Open-label, Multicentre Phase III Clinical Study to Evaluate the Efficacy and Safety of JS105 Combined With Dalpiciclib and Fulvestrant Compared With Dalpiciclib and Fulvestrant in Patients With PIK3CA-mutated, HR-positive, HER2-negative Recurrent or Metastatic Breast Cancer.

This study is a randomised, open-label, multicentre phase III clinical study evaluating the efficacy and safety of JS105 combined with Dalpiciclib and Fulvestrant compared with Dalpiciclib and Fulvestrant in patients with PIK3CA-mutated, HR-positive, HER2-negative recurrent or metastatic breast cancer.

Inclusion Criteria:

1. At the time of signing the consent form, age must be between 18 and 75 years old, males and females;
2. Patients with unresectable PIK3CA-mutated HR-positive HER2-negative recurrent or metastatic breast cancer;
3. Consent to provide tumour tissue or blood samples to determine the PIK3CA mutation status;
4. ECOG 0 or 1;
5. At least one measurable lesion as per RECIST v1.1, or only bone metastases;
6. Expected survival≥12 weeks;
7. Good organ function;
8. Patients voluntarily join the study and sign the informed consent;

Exclusion Criteria:

1. Previously treated with fulvestrant or PI3K/AKT/mTOR inhibitors;
2. Presence of untreated or active central nervous system (CNS) metastases;
3. Presence of significant clinical symptoms or uncontrolled pleural effusion, ascites, or pericardial effusion that require repeated drainage (once a month or more frequently);
4. Untreated spinal cord compression, or previously treated spinal cord compression without clinical evidence of disease stability for at least 4 weeks prior to the first study treatment;
5. Have received other anti-tumor treatment within 2-4 weeks before the first dose;
6. Toxicities from prior anti-tumor therapy that have not recovered to ≤ Grade 1;
7. Coexisting uncontrolled accompanying diseases, including but not limited to: history of type I diabetes or uncontrolled type II diabetes, presence of active infection, severe cardiovascular or cerebrovascular diseases, etc;
8. Having another malignant tumour within the last 5 years prior to the first study treatment, except for malignancies that are expected to be cured after treatment;
9. Active hepatitis B or C;
10. Known hypersensitivity to any of the study drugs or their excipients;
11. Pregnant or breastfeeding females;
12. Presence of other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participation in the study, affect treatment compliance, or interfere with study results, as judged by the investigator;