An Open-Label, Randomized Phase III Study of Trastuzumab Rezetecan With or Without Bevacizumab in First to Third Line BLIS Subtype TNBC (TRIBE)

A Randomized Phase III Study of Trastuzumab Rezetecan With or Without Bevacizumab as First- to Third-Line Treatment for Basal-like Immune-suppressed Triple-Negative Breast Cancer

This study is a prospective, open-label, phase III, randomized controlled clinical trial. It is planned to screen patients with inoperable locally advanced or metastatic triple-negative breast cancer of the BLIS subtype. A total of 140 patients are planned to be enrolled.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Triple Negative Breast Cancer (TNBC)
• Intervention / Treatment: Drug: SHR-A1811+BEV; Drug: SHR- A1811

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yin Liu; Phone Number: 02164175590; Email: liuyinfudan@163.com
• Study Contact Backup: Name: Zhimin Shao; Phone Number: 02164175590; Email: zhimingshao@yahoo.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤70 years;
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
3. Life expectancy of at least 3 months;
4. Histologically confirmed invasive triple-negative breast cancer (defined as breast cancer with estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER-2] all determined to be negative by pathological testing. Specifically: ER-negative: IHC <1%; PR-negative: IHC <1%; HER2-negative: IHC -/+ or IHC ++ with FISH/CISH negative. All specimens must be verified as the BLIS subtype of the Fudan quadruple molecular classification by the Precision Medicine Center/Department of Pathology at the study's participating center);
5. Tumor stage: recurrent or metastatic breast cancer; for locally recurrent disease, radical surgical resection must be confirmed by the investigator to be not feasible. Number of prior lines of therapy in the advanced setting ≤2;
6. Patients must have at least one lesion (measurable and/or non-measurable) that has not been previously irradiated, can be accurately assessed at baseline by CT/MRI, and can be repeatedly evaluated according to RECIST 1.1;

7. Adequate major organ function, meeting the following criteria:

   Hematological parameters: hemoglobin (HB) ≥90 g/L (without blood transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×10⁹/L; platelet count (PLT) ≥75×10⁹/L;Biochemical parameters: total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; in the presence of liver metastases, ALT and AST ≤5×ULN; serum creatinine (Cr) ≤1×ULN, and calculated creatinine clearance >50 mL/min (Cockcroft-Gault formula);

8. No prior radiotherapy, endocrine therapy, molecular targeted therapy, or surgery within 3 weeks before study initiation, and recovery from acute toxicities of prior treatment (if surgery was performed, the wound must be completely healed); no peripheral neuropathy or only grade I peripheral neurotoxicity;
9. Female subjects of childbearing potential must agree to use a medically accepted contraceptive method during the study treatment period and for at least 3 months after the last dose of study drug;
10. Subjects must voluntarily participate in this study, sign the informed consent form, have good compliance, and be willing to cooperate with follow-up.

Exclusion Criteria:

• Patients with any of the following criteria will be excluded from this study:

  1. Known central nervous system (CNS) metastases or a history of CNS metastases prior to screening. For patients with clinically suspected CNS metastases, contrast-enhanced CT or contrast-enhanced magnetic resonance imaging (MRI) must be performed within 28 days before the first dose to rule out CNS metastases;
  2. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina pectoris, myocardial infarction within the past 6 months, or ventricular arrhythmias;
  3. Persistent adverse events of Grade ≥1 resulting from prior treatment. Exceptions to this are alopecia or conditions that the investigator deems should not preclude enrollment. Such cases should be clearly documented in the investigator's notes;
  4. Major surgery (excluding minor procedures such as placement of vascular access) within 3 weeks before the first cycle of study treatment;
  5. Pregnant or lactating patients;
  6. Other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin;
  7. Presence of third-space fluid accumulation (e.g., massive pleural effusion or ascites) that cannot be controlled by drainage or other methods;
  8. Participation in another anti-tumor drug clinical trial within 3 weeks before the first use of the study drug;
  9. Long-term unhealed wounds or incompletely healed fractures;
  10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or HBV DNA ≥500 IU/mL, or chronic hepatitis with abnormal liver function;
  11. History of allergic constitution, known allergy to any component of the study drug regimen, or history of allergy to other monoclonal antibodies;
  12. History of gastrointestinal bleeding within the past 6 months, or clear evidence of a tendency for gastrointestinal bleeding, such as esophageal varices at risk of bleeding, active local ulcerative lesions, or fecal occult blood test ≥ (++). Patients with fecal occult blood test (+) should undergo gastroscopy;
  13. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to study enrollment;
  14. Urinalysis showing urine protein ≥ (++), or confirmed 24-hour urine protein quantification >1.0 g;
  15. Hypertension that cannot be controlled to within normal range with antihypertensive medication (systolic blood pressure >140 mmHg, diastolic blood pressure >90 mmHg);
  16. Prior use of anti-angiogenic agents or prior exposure to an antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as the payload

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: Arm-A; SHRA1811 at 4.8 mg/kg in combination with BP102 at 15 mg/kg, administered by intravenous infusion on Day 1, with a 3-week treatment cycle.	Drug: SHR-A1811+BEV; SHRA1811(HER-targeted ADC) at 4.8 mg/kg in combination with BEV(bevacizumab) at 15 mg/kg, administered by intravenous infusion on Day 1, with a 3-week treatment cycle.; Other Names: Trastuzumab Rezetecan；bevacizumab
Active Comparator: Arm-B; SHRA1811 at 4.8 mg/kg, administered by intravenous infusion on Day 1, with a 3-week treatment cycle.	Drug: SHR- A1811; SHRA1811(HER-targeted ADC) 4.8 mg/kg, administered via intravenous infusion on Day 1 of each 3-week cycle.; Other Names: Trastuzumab Rezetecan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival(PFS)	Time to progressive disease (according to RECIST1.1)	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions	24 months
Duration of Response (DoR)	the time from the first documented objective response (complete response or partial response) to the first documented disease progression or death from any cause, whichever occurs first.	24 months
Disease Control Rate (DCR)	The proportion of evaluable patients who achieve Complete Response (CR) , Partial Response (PR) , or Stable Disease (SD) after treatment.	24 months
Overall survival (OS)	Time from the enrollment to death of any cause	24months
Safety and Tolerability	Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria.	24months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: June 20, 2026
• First Submitted That Met QC Criteria: June 20, 2026
• First Posted (Actual): June 25, 2026

Study Record Updates

• Last Update Posted (Actual): June 25, 2026
• Last Update Submitted That Met QC Criteria: June 20, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: 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
• Other Study ID Numbers: SCHBCC-N0116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No