A Phase II Study of SSGJ-612 Plus a HER2-Targeted ADC in HR-Positive, HER2-Low or HER2-Ultralow Expression Metastatic Breast Cancer

The study is divided into two parts: Participants in Part 1: Breast cancer patients who have received at least one line of chemotherapy for metastatic disease; Participants in Part 2: Breast cancer patients who have not received any chemotherapy for metastatic disease.

Inclusion criteria

• Voluntary participation in this study, signed informed consent form, good treatment compliance, and willingness to cooperate to complete all trial procedures.
• Expected survival duration ≥ 3 months.
• Histopathologically confirmed breast cancer meeting all of the following criteria simultaneously:

• Metastatic tumor;
• Tumor samples tested by central laboratory confirmed as HER2-low or HER2 ultra-low expression;
• No prior test results reporting HER2 positivity;
• Tumor sample testing confirms hormone receptor-positive (HR+) status.
• Patients must satisfy either of the following conditions:

• Disease progression within 6 months after initiation of first-line endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors for metastatic disease;
• Received at least 2 lines of prior endocrine therapy for metastatic disease, with disease progression post-treatment.
• Participants in Part 1: Breast cancer patients who have received at least one line of chemotherapy for metastatic disease; Participants in Part 2: Breast cancer patients who have not received any chemotherapy for metastatic disease.
• At least one repeatedly and accurately measurable tumor lesion as target lesion assessed per RECIST v1.1 criteria.

Exclusion criteria

• Uncontrolled or severe cardiovascular disease.
• History of interstitial lung disease (ILD)/pneumonia requiring corticosteroid therapy (non-infectious), or current ILD/pneumonia, or suspected ILD/pneumonia not excluded by screening imaging.
• Presence of pulmonary-specific, clinically significant comorbid conditions.
• Presence of spinal cord compression, or clinically active central nervous system metastases.
• Female patients who are pregnant, breastfeeding, or planning pregnancy.
• Patients who received investigational drug therapy in another clinical trial within 30 days prior to first study drug administration, or who are concurrently enrolled in another clinical trial. Note: Exclusions include participation in observational (non-interventional) clinical trials, or being in the follow-up phase of an interventional clinical trial.
• Presence of drug abuse, or other diseases (e.g., psychiatric disorders) that, in the investigator's judgment, may interfere with patient participation in the trial or affect the assessment of trial outcomes.