Adding JS105 to dalpiciclib and fulvestrant for 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 trial tests whether adding JS105 to dalpiciclib plus fulvestrant helps people with PIK3CA‑mutated, hormone receptor‑positive, HER2‑negative recurrent or metastatic breast cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 312 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Risen (Suzhou) Pharma Tech Co., Ltd. (Industry-sponsored)
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07207070 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label, multicentre Phase III comparison of JS105 plus dalpiciclib and fulvestrant versus dalpiciclib and fulvestrant alone in adults with PIK3CA‑mutated, HR‑positive, HER2‑negative recurrent or metastatic breast cancer. Eligible patients are 18–75 years old with ECOG 0–1 and at least one measurable lesion or bone‑only metastases and must provide tumor tissue or blood for PIK3CA testing. Key exclusions include prior fulvestrant or PI3K/AKT/mTOR inhibitor treatment and untreated or active CNS metastases or significant uncontrolled effusions. The trial measures efficacy and safety outcomes to determine whether the three‑drug combination provides better disease control than the two‑drug regimen.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–75 with unresectable PIK3CA‑mutated, HR‑positive, HER2‑negative recurrent or metastatic breast cancer, ECOG 0–1, measurable disease or bone‑only metastases, and no prior fulvestrant or PI3K/AKT/mTOR inhibitor therapy.

Not a fit: Patients previously treated with fulvestrant or PI3K/AKT/mTOR inhibitors, those with untreated or active CNS metastases, or those with significant uncontrolled effusions or spinal cord compression are unlikely to qualify or benefit from this trial.

Why it matters

Potential benefit: If successful, adding JS105 could improve disease control or delay progression for patients with PIK3CA‑mutant HR‑positive, HER2‑negative metastatic breast cancer.

How similar studies have performed: Related approaches combining targeted agents with endocrine therapy have shown benefit in PIK3CA‑mutant HR‑positive breast cancer (for example alpelisib with endocrine therapy), but triple combinations like this remain under active study.

Eligibility criteria

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;

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Chinese Acadamy of Medical Sciences and Peking Union Medical College — Beijing, Beijing Municipality, China (Recruiting)
• Henan Provincial Cancer Hospital — Zhengzhou, Henan, China (Recruiting)

Study contacts

• Study coordinator: Qianna Zhan, Master

Conditions Breast Cancer