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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Stage IV; Triple -Negative Breast Cancer
• Intervention / Treatment: Drug: Camrelizumab+Apatinib+Eribulin; Drug: Physician's choice chemotherapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 246
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jieqiong Liu, M.D., Ph.D.; Phone Number: +86-020-34071156; Email: liujieqiong01@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital of Shanghai
    • Contact: Hengyu Li, Dr.; Phone Number: +86 21 31166666
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-Sen Memorial Hospital
      • Contact: Jieqiong Liu, M.D., Ph.D.; Phone Number: +86-020-34071156; Email: liujieqiong01@163.com
      • Principal Investigator: Jieqiong Liu, M.D., Ph.D
  • Guizhou
    • Guiyang, Guizhou, China
      • Recruiting
      • The Affiliated Hospital of Guizhou Medical University
      • Contact: Shu Liu, M.D., Ph.D.; Phone Number: +86-851-86855119
      • Principal Investigator: Shu Liu, M.D., Ph.D
  • Hubei
    • Wuhan, Hubei, China
      • Not yet recruiting
      • Wuhan Union Hospital of China
      • Contact: Yanxia Zhao, M.D., Ph.D.; Phone Number: +86-027-85726114
      • Principal Investigator: Yanxia Zhao, M.D., Ph.D
    • Yichang, Hubei, China
      • Recruiting
      • Yichang Central People's Hospital
      • Contact: Yuyan Tan, M.D., Ph.D.; Phone Number: +86-0717-6484621
      • Principal Investigator: Yuyan Tan, M.D., Ph.D
  • Hunan
    • Changsha, Hunan, China
      • Not yet recruiting
      • Xiangya Hospital of Central South University
      • Contact: Kejing Zhang, M.D., Ph.D.; Phone Number: +86-0731-82650001
      • Principal Investigator: Kejing Zhang, M.D., Ph.D
    • Yongzhou, Hunan, China
      • Recruiting
      • The Central Hospital Of Yong Zhou
      • Contact: Sijuan Ding; Phone Number: +86-0746-6565666
      • Principal Investigator: Sijuan Ding, M.D., Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Camrelizumab (200 mg, IV, Day 1) + Apatinib (250 mg, PO, QD) + Eribulin (1.4 mg/m², IV, Day 1 and Day 8) administered in 21-day cycles.	Drug: Camrelizumab+Apatinib+Eribulin; Camrelizumab (200 mg, IV, Day 1) + Apatinib (250 mg, PO, QD) + Eribulin (1.4 mg/m², IV, Day 1 and Day 8) administered in 21-day cycles.
Active Comparator: Control Group; Physician's Choice Chemotherapy	Drug: Physician's choice chemotherapy; Physician's Choice Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Disease evaluation will be performed according to RECIST v1.1 criteria.	Time from enrollment to the occurrence of predefined events, including disease progression or death, whichever came first, assessed up to 60 months.
Overall Survival	Death from any cause.	From date of randomization until the date of death from any cause, assessed up to 120 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The percentage of patients in different groups whose tumor size reduction, meets the criteria for complete response (CR) or partial response (PR).	From date of randomization until the date of first documented CR or PR, whichever came first, assessed up to 12 months.
Disease control rate	Proportion of patients achieving CR, PR, or stable disease (SD).	From date of randomization until the date of first documented CR, PR or SD, assessed up to 12 months.
Clinical Benefit Rate	Proportion of patients achieving CR, PR, or SD.	From date of randomization until the date of first documented CR, PR or SD for more than 6month, assessed up to 18 months.
Duration of Response	Time from the first assessment showing CR or PR to the first occurrence of progressive disease (PD) or death from any cause.	Time from the first assessment showing CR or PR to the first occurrence of PD or death from any cause, whichever came first, assessed up to 120 months.
Time to Response	Time from randomization to the first occurrence of CR or PR.	Time from randomization to the first occurrence of CR or PR, whichever came first, assessed up to 6 months
Two-Year Overall Survival Rate	Proportion of patients alive two years after randomization.	Two years after randomization.
Safety Evaluation	Comparison of the incidence and severity of adverse events between the two groups.	From randomization to 30 days after the last dose of study treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor and Peripheral Blood Biomarker Analysis	This analysis aims to identify biomarkers that predict treatment response, resistance, and prognosis in advanced triple-negative breast cancer (TNBC). Tumor Biomarker Analysis: Genetic and Molecular Profiling: Whole-exome sequencing (WES), RNA sequencing, and proteomics to identify mutations, gene expression patterns, and protein markers related to treatment response. Immune Microenvironment Assessment: Immunohistochemistry (IHC) and multiplex immunofluorescence to evaluate tumor-infiltrating lymphocytes (TILs), PD-L1 expression, and other immune-related markers. Peripheral Blood Biomarker Analysis: Measurement of inflammatory and immunomodulatory cytokines to assess systemic immune response.	Before treatment and after 2 cycles (each cycle is 21 days) of treatment, or disease progression.
QoL	Quality of life assessment will be conducted using the EORTC QLQ-BR23 questionnaire. Raw scores will be linearly transformed to a standardized scale ranging from 0 to 100 points.	At baseline upon enrollment and every 2cycles (each cycle is 21 days) of treatment, from date of randomization until the patient exits the study due to disease progression, adverse events, whichever came first, assessed up to 60 months.

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: March 11, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 21, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Advanced Triple-Negative Breast Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: CAPER-III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No