Sacituzumab Tirumotecan Plus Anlotinib for Metastatic Triple Negative Breast Cancer

Inclusion Criteria:

• Age ≥ 18 years at the time of signing informed consent.

• Histologically and/or cytologically confirmed triple-negative breast cancer (TNBC)based on the most recent biopsy or pathological specimen, including:

1. Definition of human epidermal growth factor receptor 2 (HER2) negative:immunohistochemistry (IHC) of 0 or 1+; if HER is 2+ by IHC, negative HER2expression must be confirmed by fluorescence in situ hybridization (FISH);

2. Estrogen and progesterone receptor negative means that less than 1% of thecells express hormone receptors as indicated by IHC.

• Patients with unresectable locally advanced or metastatic triple-negative breastcancer who have received at least one line of standard of care regimens, including:

1. Any treatment received by the patients regardless of triple-negative state canbe included as one of the standard of care regimens;

2. For neoadjuvant and/or adjuvant chemotherapy, if relapse or disease progressionto unresectable locally advanced or metastatic disease occurs during treatmentor within 12 months after discontinuation of treatment (at least 2 cycles havebeen completed), it will be considered as one of the standard of care regimens;

3. For patients with documented germline BRCA1/BRCA2 mutations, if they have beentreated with an approved PARP inhibitor, then the PARP inhibitor can beconsidered as one prior standard of care regimens required;

4. Patients must have progressed on or were intolerable to the treatment during orafter the last treatment prior to enrollment.

• Newly diagnosed brain metastases at screening must be stable for ≥4 weeks afterlocal treatment (e.g., radiotherapy) with imaging confirmation.

• Patients must have at least one measurable lesion per RECIST v1.1 criteria; thosewith only skin or bone lesions cannot be included.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

• With an expected survival of ≥ 12 weeks.

• Patients must have adequate organ and bone marrow function (no blood transfusion,recombinant human thrombopoietin, or colony stimulating factor therapy has beenreceived within 2 weeks prior to the treatment), which is defined as follows:

1. Hematology: neutrophil count (NEUT) ≥ 1.5 × 10^9/L; platelets (PLT) ≥ 100 × 10^9/L; hemoglobin ≥ 90g/L;

2. Liver function: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), for patients with liver metastases,ALT and AST must be ≤ 5 × ULN; Albumin ≥ 30g/L; total bilirubin (TBIL) ≤ 1.5 ×ULN;

3. Renal function: creatinine clearance (Ccr) ≥ 50 ml/min;

4. Coagulation function: international normalized ratio (INR), activated partialthromboplastin time (APTT) and prothrombin time (PT) ≤ 1.5 × ULN.

• Patients of childbearing potential (male or female) must use effective medicalcontraception from consent until 6 months after the end of the dosing period.

• Patients voluntarily participate in the study, sign the informed consent form, andwill be able to comply with the protocol-specified visits and relevant procedures.

Exclusion Criteria:

• Previously received any of the following treatments (including in the adjuvant orneoadjuvant setting):

1. TargetedTROP2therapy;

2. Any drug treatment targeting topoisomeraseI, including antibody-drug conjugates (ADC) therapy;

3. Anti-angiogenic drugtherapy.

• Patients with multiple factors affecting oral medication.

• Known to have meningeal metastasis, brainstem metastasis, spinal cord metastasis,and/or compression, active central nervous system (CNS) metastasis. Patients withpreviously treated brain metastases can participate if clinically stable for atleast 4 weeks before dosing and do not require corticosteroids or anticonvulsantsfor at least 14 days. Patients with untreated asymptomatic brain metastases mustrequire investigator approval.

• Within 3 years before administration having other malignancies (except for thosecured by local treatment, such as basal cell carcinoma of the skin, squamous cellcarcinoma of the skin, cervical carcinoma in situ, etc.).

• Presence of any of the following cardiovascular diseases or risk factors:

1. Within 6 months before administration, myocardial infarction, unstable angina,acute or persistent myocardial ischemia, grade 3 or grade 4 heart failure,symptomatic or poorly controlled severe arrhythmias, cerebrovascular accident,transient ischemic attack, and other severe cardiovascular diseases;

2. History of myocarditis, primary cardiomyopathy, specific cardiomyopathy, andother myocardial diseases;

3. Within 3 months before administration, any deep vein thrombosis (if stabilizedby low molecular weight heparin or similar drugs≥ 2 weeks, enrollment isallowed), peripheral arterial thromboembolism, pulmonary embolism, or othersevere thromboembolic events;

4. Presence of aortic aneurysm, aortic dissection aneurysm, or other majorvascular diseases that may be life-threatening or require surgery within 6months before administration.

• Uncontrollable systemic diseases as judged by the investigator:

1. Poorly controlled diabetes (fasting blood glucose≥ 10 mmol/L on two consecutiveoccasions);

2. Poorly controlled hypertension (systolic blood pressure> 160 mmHg and/ordiastolic blood pressure> 100 mmHg);

3. Presence of clinically symptomatic or requiring repeated drainage of pleuraleffusion, pericardial effusion, or ascites (> 1 time/week).

• Presence of steroid-requiring (non-infectious) interstitial lung disease (ILD) or ahistory of non-infectious pneumonia, currently having ILD or non-infectiouspneumonia, or suspected ILD or non-infectious pneumonia that cannot be ruled out byimaging at screening.

• Clinically significant lung damage due to pulmonary complications, including but notlimited to any underlying lung disease or any autoimmune, connective tissue, orinflammatory disease that may involve the lungs, or previous total pneumonectomy.

• Patients with active chronic inflammatory bowel disease, gastrointestinalobstruction, severe ulcers, gastrointestinal perforation, abdominal abscess, oracute gastrointestinal bleeding.

• Patients with acute gastrointestinal bleeding, persistent bleeding disorders, orbleeding tendencies such as coagulopathy.

• Toxicity from previous anti-tumor treatments has not recovered to ≤ 1grade (based onNCI CTCAE v5.0 assessment) or to the level specified by the inclusion criteria (excluding toxicities such as alopecia, fatigue, etc., judged by the investigator tobe of low safety risk).

• Having an active autoimmune disease requiring systemic treatment in the past twoyears (including but not limited to: autoimmune hepatitis, uveitis, colitis,hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, etc.),systemic treatment includes disease-modifying drugs, immunosuppressants, systemiccorticosteroids (> 10 mg/day prednisone or equivalent). Hormone replacement therapy,such as thyroxine, insulin, or physiological corticosteroid replacement therapy foradrenal or pituitary insufficiency, is not considered a systemic treatment;within2weeks before administration> 10 mg/day prednisone systemic corticosteroidtreatment or other immunosuppressive drugs.

• Known active tuberculosis.

• Known history of allogeneic organ transplantation and allogeneic hematopoietic stemcell transplantation.

• With ≥ 2 grade peripheral neuropathy.

• Active hepatitis B or hepatitis C.

• Human Immunodeficiency Virus (HIV) test positive or history of AcquiredImmunodeficiency Syndrome (AIDS); known active syphilis infection.

• Known allergy to the study drug or any of its components, known history of severehypersensitivity to other biological products.

• Major surgery within 4 weeks prior to dosing or expected to require major surgeryduring the study period.

• Severe infection within 4 weeks prior to dosing, including but not limited tocomplications requiring hospitalization, sepsis, or severe pneumonia; activeinfection requiring systemic anti-infective treatment within 2 weeks prior todosing.

• Documented severe dry eye syndrome, severe meibomian gland disease and/orblepharitis, or history of corneal disease that impedes delayed corneal healing.

• Non-specific immunomodulatory treatment within 2 weeks prior to dosing (includingbut not limited to interferon,IL-2), approved traditional Chinese medicinepreparations for anti-tumor indications, etc.

• Prior to dosing 30 days after receiving a live vaccine, or planning to receive alive vaccine during the study period.

• Rapid deterioration of the condition during the screening before administration,such as significant changes in physical status.

• Pregnant or breastfeeding women.

• Suffering from local or systemic diseases caused by non-malignant tumors, ordiseases or symptoms secondary to tumors, which may lead to high medical risk and/oruncertainty in survival evaluation, such as tumor leukemic reactions, cachexiamanifestations, etc.

• Any condition that the researcher believes interferes with the evaluation of thestudy drug or the safety of the subject or the interpretation of the study results,or any other condition that the investigator believes is not suitable forparticipation in this study.