Fluorizoparib Plus Apatinib Versus Chemotherapy in HRD-positive, HER2-negative Advanced Breast Cancer

Sun Yat-sen University

Status and phase: Active, not recruiting; Phase 3

Conditions: HRD-Positive/HER2-Negative Advanced Breast Cancer; Metastatic Breast Cancer

Treatments: Drug: Apatinib; Drug: Physician's Choice Chemotherapy/ADC Regimen; Drug: Chemotherapy/ADC Regimen; Drug: Fluorizoparib

Study type: Interventional

Funder types: Other

Identifiers

NCT07371910

SYSKY-2023-1016-05

Details and patient eligibility

About

This is a Phase III clinical trial for patients with a specific type of advanced breast cancer that is HER2-negative and has a biomarker called "Homologous Recombination Deficiency (HRD)-positive."

The study aims to compare the effectiveness and safety of two treatment strategies:

Experimental Group: Patients will first receive 6 cycles of standard chemotherapy or antibody-drug conjugate (ADC) therapy chosen by their doctor. After completing these 6 cycles, they will switch to a combination of two oral targeted drugs: Fluorizoparib and Apatinib, as long-term maintenance therapy.

Control Group: Patients will continue to receive their doctor's choice of standard chemotherapy or ADC therapy without switching to the targeted drug combination.

Patients will be randomly assigned (like flipping a coin) to one of the two groups.

Enrollment: 200 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Female patients aged 18-70 years.

Histologically confirmed HER2-negative metastatic breast cancer.

Documented HRD-positive status (defined as BRCA1/2 mutation and/or HRD positive).

HR+/HER2- patients must have received prior endocrine therapy for metastatic disease.

Have received no more than 2 prior lines of chemotherapy or ADC therapy for metastatic disease.

At least one measurable lesion per RECIST 1.1.

ECOG performance status 0-2 and life expectancy ≥3 months.

Adequate organ function (bone marrow, liver, renal, cardiac).

Exclusion criteria

• HR+/HER2- patients who have not received prior endocrine therapy for metastatic disease.

Have not received any prior systemic therapy for metastatic breast cancer.

Have received >2 prior lines of chemotherapy or ADC therapy for metastatic disease.

Known severe hypersensitivity to any component of the study drugs.

Pregnant, lactating, or women of childbearing potential unwilling to use effective contraception.

Uncontrolled or significant cardiovascular disease.

Any other condition deemed inappropriate for the study by the investigato

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Sequential Fluorizoparib + Apatinib after Chemotherapy/ADC

Experimental group

Description:

This is the experimental arm. Participants receive a two-phase sequential treatment strategy: Induction Phase: 6 cycles of investigator-selected chemotherapy or ADC therapy. Maintenance Phase: Participants who complete induction without disease progression switch to long-term oral maintenance therapy with the combination of Fluorizoparib and Apatinib. Treatment continues until disease progression, unacceptable toxicity, withdrawal, or death.

Treatment:

Drug: Fluorizoparib

Drug: Chemotherapy/ADC Regimen

Drug: Apatinib

Physician's Choice Chemotherapy/ADC Regimen

Active Comparator group

Description:

This is the control arm intervention. Participants receive continuous treatment with a standard chemotherapy regimen or an Antibody-Drug Conjugate (ADC) selected by the investigator from protocol-specified options (e.g., eribulin, vinorelbine, gemcitabine, capecitabine, sacituzumab govitecan, or trastuzumab deruxtecan). Treatment is administered intravenously or orally according to the standard schedule of the chosen agent and continues without a planned switch to the oral targeted combination therapy, until disease progression, unacceptable toxicity, withdrawal of consent, or death.

Treatment:

Drug: Physician's Choice Chemotherapy/ADC Regimen