Phase III Trial of Camrelizumab+Apatinib+Eribulin vs. Physician's Choice Chemotherapy in Advanced Triple-Negative Breast Cancer

A Multicenter, Phase III, Randomized Controlled Trial Comparing Camrelizumab Plus Apatinib and Eribulin Versus Physician's Choice Chemotherapy in the Treatment of Advanced Triple-Negative Breast Cancer

This study evaluates the efficacy and safety of camrelizumab, apatinib, and eribulin versus physician's choice chemotherapy in advanced TNBC.Primary Objectives: Assess improvements in progression-free survival (PFS) and overall survival (OS).Secondary Objectives: Compare objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), time to response (TTR), two-year OS rate, biomarker analysis, and quality of life (QoL).Safety: Assess and compare adverse event incidence and severity.

This study aims to evaluate the efficacy and safety of the triplet regimen compared to physician's choice chemotherapy as a later-line treatment for advanced triple-negative breast cancer (TNBC). 1. Primary Objectives and Endpoints: To determine whether the combination of camrelizumab, apatinib, and eribulin improves progression-free survival (PFS) and overall survival (OS) compared to investigator's choice chemotherapy in advanced TNBC. 2. Secondary Objectives and Endpoints: To compare the following clinical parameters between the camrelizumab, apatinib, and eribulin combination and investigator's choice chemotherapy for advanced TNBC: -Objective response rate (ORR) Disease control rate (DCR) Clinical benefit rate (CBR) Duration of response (DoR) Time to response (TTR) Two-year overall survival rate (2-year OS rate) Biomarker analysis Quality of life (QoL) analysis 3.Safety Evaluation: Comparison of the incidence and severity of adverse events between the two groups.

Inclusion Criteria:

1. The subject voluntarily agrees to participate in this study and signs an informed consent form (ICF).
2. Female subjects aged ≥18 and ≤70 years on the date of signing the ICF.
3. Pathologically confirmed advanced triple-negative breast cancer (TNBC), defined as ER-negative (IHC ER-positive percentage <1%), PR-negative (IHC PR-positive percentage <1%), and HER2-negative (IHC-/+, or IHC++ but FISH/CISH-), with at least one measurable lesion per RECIST v1.1 criteria.
4. Patients who have received at least 1 and up to 4 lines of prior systemic therapy for metastatic or locally advanced unresectable triple-negative breast cancer (TNBC) with disease progression. Prior systemic therapy (including at least 1 line of chemotherapy and neoadjuvant/adjuvant chemotherapy) must include at least a taxane or anthracycline. Subjects who relapse within 6 months after completion of neoadjuvant/adjuvant chemotherapy are considered as having failed first-line therapy.
5. Capable of swallowing tablets.
6. ECOG performance status of 0-1.
7. Expected survival ≥12 weeks.
8. Adequate function of vital organs, meeting the following criteria (without the use of blood products or growth factors during the screening period): Absolute neutrophil count (ANC) ≥1.5×10⁹/L. Platelet count ≥100×10⁹/L. Hemoglobin ≥9 g/dL. Serum albumin ≥3 g/dL. Thyroid-stimulating hormone (TSH) ≤ULN (if abnormal, T3 and T4 levels should be assessed; subjects with normal T3 and T4 levels are eligible). Total bilirubin ≤1.0×ULN (for subjects with Gilbert's syndrome or liver metastases, total bilirubin ≤1.5×ULN). ALT and AST ≤1.5×ULN (for subjects with liver metastases, ≤3×ULN). Alkaline phosphatase (ALP) ≤2.5×ULN. Renal function within 7 days prior to the first dose: serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min.
9. Women of childbearing potential agree to use highly effective contraception starting at least 7 days prior to the first dose and continuing for 24 weeks after the last dose. A negative serum pregnancy test is required within 7 days prior to the first dose.

Exclusion Criteria:

1. Subjects with untreated active brain metastases or leptomeningeal metastases.
2. Participation in any other interventional clinical trial within 28 days prior to the first dose.
3. History of severe allergic reactions to other monoclonal antibodies.
4. Receipt of other antitumor therapies within 28 days prior to the first dose.
5. Uncontrolled hypertension despite antihypertensive medication (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg).
6. Prior treatment with CTLA-4, Tim-3, or LAG-3 antibodies, or T-cell co-stimulatory therapies (previous use of PD-1 or PD-L1 antibodies is allowed).
7. Prior treatment with anti-angiogenic agents or eribulin chemotherapy.
8. Presence of any active autoimmune disease or a history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism). Subjects with vitiligo, or childhood asthma that has fully resolved without intervention in adulthood, may be included. Subjects with asthma requiring medical intervention with bronchodilators are excluded.
9. Uncontrolled cardiac clinical symptoms or diseases, including: Heart failure classified as NYHA Class II or higher. Unstable angina. Myocardial infarction within the past year. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
10. Urinalysis indicating proteinuria ≥++ or confirmed 24-hour urinary protein ≥1.0 g.
11. Known hereditary or acquired bleeding or thrombotic disorders (e.g., hemophilia, coagulopathy, thrombocytopenia, hypersplenism).
12. Congenital or acquired immunodeficiency (e.g., HIV infection).
13. Receipt of a live vaccine within 4 weeks prior to or during the study period.
14. Allergy or contraindication to the investigational drugs.
15. Underwent surgery within 3 months prior to enrollment or anticipated need for major surgical procedures during the study period.