Fluzoparib plus apatinib versus physician-selected chemotherapy for HRD-positive, HER2-negative advanced breast cancer

Randomized, Open, Controlled, Multicenter Phase III Clinical Study of Fluzoparib in Combination With Apatinib Versus Investigator-Selected Chemotherapy for HRD-Positive/HER2-negative Advanced Breast Cancer

This trial will test whether combining the PARP inhibitor fluzoparib with the anti-angiogenic drug apatinib works better than doctors' choice chemotherapy for adults with HRD-positive, HER2-negative advanced breast cancer.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University (other)
• Drugs / interventions: chemotherapy, apatinib, abatinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06255392 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, phase III trial comparing the oral PARP inhibitor fluzoparib plus the anti-angiogenic agent apatinib against investigator-selected chemotherapy in patients with HRD-positive, HER2-negative metastatic breast cancer. Eligible patients are adults with HER2-negative disease who test HRD-positive (BRCA1/2 mutation or HRD score ≥42) and have received no more than two prior lines of chemotherapy for metastatic disease. The trial builds on preclinical data and prior ovarian cancer work suggesting synergy between PARP inhibition and anti-angiogenesis, aiming to expand targeted combination therapy beyond BRCA-mutant cases. Outcomes will determine whether this combination improves clinical benefit compared with standard chemotherapy in this biomarker-selected population.

Who should consider this trial

Good fit: Ideal candidates are adult women (18–70 years) with metastatic HER2-negative breast cancer who are HRD-positive (BRCA1/2 mutation or HRD score ≥42), have ECOG ≤2, at least one measurable lesion, and have received no more than two prior lines of chemotherapy for metastatic disease.

Not a fit: Patients who are HRD-negative, HER2-positive, have received more than two prior lines of metastatic chemotherapy, or have poor performance status are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could provide HRD-positive/HER2-negative patients a new targeted treatment option that may shrink tumors or delay disease progression.

How similar studies have performed: Similar PARP inhibitor plus anti-angiogenic combinations have shown benefit in ovarian cancer and encouraging signals in early-phase breast cancer work, but this phase III trial seeks definitive evidence in HRD-positive/HER2-negative breast cancer.

Eligibility criteria

Inclusion criteria

The subjects must meet all of the following conditions:

Adult female patients (aged 18 to 70 years) with metastatic breast cancer diagnosed by pathology or imaging; 2) Pathological confirmation of HER2 negative (definition: immunohistochemical result is 0 or + or ++ and in situ hybridization result is negative); 3) The patient's HRD test was positive (definition: BRCA1/2 mutation, or HRD score greater than or equal to 42 points); 4) HR+/HER2- patients who have received endocrine therapy during the metastasis stage; 5) Having received no more than two lines of chemotherapy (or ADC) regimens for metastatic breast cancer in the past; 6) Evaluation of anti-tumor treatment (including chemotherapy /HER2-ADC/TROP2-ADC) for 6-8 cycles to achieve clinical benefit (CR or PR) or SD for 24 weeks or more; 7) ECOG physical condition score ≤2 points, and the expected survival period is no less than 3 months; 8) At least one measurable lesion was found in the imaging examination within 2 weeks before enrollment. Or simple bone metastasis lesion; 9) At the time of enrollment, the previous treatment-related toxicity must be remitted to NCI CTCAE (Version 5.0) ≤1 degree (except for alopecia or other toxicities that the investigator deems to pose no risk to the patient's safety).

10\) Adequate bone marrow functional reserve:

1. White blood cell count (WBC) ≥3.0×10\^9 / L
2. Neutrophil count (ANC) ≥1.5×10\^9 / L
3. Platelet count (PLT) ≥70×10\^9 / L 11) Liver, kidney and heart function tests are basically normal (based on the normal values in the laboratories of each research center) :

a. Total bilirubin (TBIL) ≤3× upper limit of normal (ULN) b. Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤2.5×ULN (≤5 ×ULN for patients with liver metastasis) c. Serum creatinine ≤1.5×ULN or creatinine clearance rate (Ccr) ≥60 ml/min; d.Left ventricular ejection fraction (LVEF) ≥ 55%, e. QTcF(Fridericia correction) ≤ 470 ms. 12) Be able to understand the research process, voluntarily participate in this research, and sign the informed consent form.

Exclusion Criteria

If a subject experiences any of the following situations, they will not be eligible to participate in this study:

1. Patients with HR+/ HER2-MBC who have not received endocrine therapy before;
2. Has not received any treatment for metastatic breast cancer;
3. Received more than two chemotherapy regimens for metastatic breast cancer;
4. Patients who are known to be allergic to the active ingredient or other ingredients of the investigational drug.
5. Pregnant or lactating women, and women of childbearing age who refused to take effective contraceptive measures during the study period.
6. Those with severe heart disease or discomfort, expected to be unable to tolerate chemotherapy, including but not limited to: fatal arrhythmia or higher-grade atrioventricular block, unstable angina pectoris, clinically significant valvular heart disease, electrocardiogram showing transmural myocardial infarction, uncontrollable hypertension;
7. Any other circumstances where the researcher deems the patient unsuitable for participation in this study, any concomitant diseases or conditions that may interfere with participation in the study, or any serious medical conditions that may affect the safety of the subjects (such as uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection).

Where this trial is running

Guangzhou, Guangdong

• Sun Yat Sen Memorial Hospital，Sun Yat sen University — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Jianli Zhao — Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Study coordinator: Zhao Jianli

Conditions: Fludzoparib&#34, and Anti-angiogenic, HRD-positive/HER2-negative Advanced Breast Cancer