A Clinical Trial to Evaluate the Efficacy and Safety of TQB2102 for Injection Versus Investigator-Selected Chemotherapy in HER2 Low-Expressing Recurrent/Metastatic Breast Cancer

The study is a Phase III, randomized, multicenter, open-label study in HER2-low, HR+ metastatic breast cancer subjects who are patients with locally advanced or metastatic breast cancer with low HER2 expression in the recurrent metastatic stage who have not received chemotherapy. The primary objective of the study is to determine the efficacy and safety of TQB2102 compared to investigator-selected single-agent chemotherapy in the target population. 542 subjects with HER2 immunohistochemistry (IHC )2+/ in situ hybridization (ISH)- and IHC 1+ (HER2-low) expression will be enrolled in 1:1 randomized groups to receive TQB2102 or investigator's choice of single-agent chemotherapy (capecitabine, paclitaxel, or albumin-paclitaxel) until progression of disease (PD), as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1. 1, unless there are unacceptable toxicity, withdrawal of consent, or meeting other discontinuation criteria.


Eligibility Criteria:
Inclusion Criteria:

* Subjects voluntarily enrolled in this study with good compliance;
* Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0-1;
* Pathologically confirmed locally advanced or metastatic breast cancer with low HER2 expression and unresectable:
* Defined hormone receptor (HR) status.
* Imaging-confirmed disease progression (during or after completion of the most recent treatment);
* Have at least one measurable lesion according to RECIST 1.1 criteria;
* Good major organ function.

Exclusion Criteria:

* The presence or current concurrent presence of other malignant tumors within 5 years prior to randomization. ;
* Unresolved toxic reactions above Common Terminology Criteria for Adverse Events (CTC AE) grade 1 due to any prior therapy;
* Major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of the pre-randomization period;
* Prolonged unhealed wounds or fractures;
* Previous history of interstitial lung disease/pneumonia requiring steroidal drug intervention;
* The presence of moderate to severe pulmonary dysfunction/disease within 3 months prior to randomization;
* The presence of an arterial/deep vein thrombotic event within 6 months prior to randomization;
* The presence of a medical condition that interferes with intravenous administration, intravenous blood collection, or inability to swallow, chronic diarrhea, intestinal obstruction, or the presence of other factors that interfere with the administration and absorption of medications;
* The presence of grade ≥2 myocardial ischemia or myocardial infarction, cardiac arrhythmias (including QT corrected (QTc) ≥450ms (men) and QTc ≥470ms (women)) and grade ≥2 congestive heart failure (New York Heart Association (NYHA) classification); angina pectoris requiring antianginal medication; and clinically significant heart valve disease;
* Active or uncontrolled ≥ CTC AE grade 2 infection present within 14 days prior to randomization;
* Cirrhosis of the liver, active hepatitis that is not well controlled;
* Renal failure requiring hemodialysis or peritoneal dialysis;
* History of immunodeficiency, including HIV-positive or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
* Those with routine urinalysis suggestive of urinary protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g;
* Those who have used immunosuppressive or systemic hormone therapy for immunosuppression within 2 weeks prior to randomization;
* Those with a history of psychotropic substance abuse that cannot be abstained from or those with psychiatric disorders;
* Tumor-related symptoms and treatments:

  1. Subjects who have been treated with other antineoplastic agents such as chemotherapy, radical radiotherapy, or immunotherapy within 4 weeks prior to randomization, or who are still within 5 half-lives of the drug (whichever occurs shortest);
  2. Treatment with endocrine therapy, molecularly targeted therapy, or a proprietary Chinese medicine with an anti-tumor indication as specified in the National Medical Products Administration (NMPA) approved drug insert within 2 weeks prior to randomization;
  3. Presence of carcinomatous lymphadenitis, or uncontrollable pleural effusion, ascites, and pericardial effusion of moderate volume or greater that requires repeated drainage to relieve clinical symptoms, or who have received drainage of plasmapheresis for therapeutic purposes within 2 weeks prior to randomization;
  4. Known carcinomatous meningitis or clinically active central nervous system metastases;
  5. Severe bone damage resulting from tumor bone metastases;
* Those who have received a control chemotherapeutic agent of the investigator's choice during the recurrent metastatic phase or for whom a control chemotherapeutic agent of the investigator's choice is inappropriate for reasons such as intolerance or contraindication to that agent;
* Has received prior anti-HER2 therapy;
* Who have developed hypersensitivity to humanized monoclonal antibody products;
* Those who have developed an allergy to any of the study drugs or any component or excipient in the drugs;
* Who have participated in and used another antitumor clinical trial drug within 4 weeks prior to randomization;
* Subjects who, in the judgment of the investigator, have a concomitant disease that seriously jeopardizes the safety of the subject or interferes with the completion of the study, or who are deemed to have other reasons for being unsuitable for enrollment.