Pucotenlimab and Anlotinib in Combination With Chemotherapy

Prior treatment

• Prior systemic anticancer therapy (including investigational agents) before planned start of study treatment.
• Major surgery, open biopsy, or significant trauma within 4 weeks prior to planned start of study treatment. Major surgery defined as requiring at least 3 weeks of recovery before study treatment.

Other illness

• Known hypersensitivity to pucotenlimab, nab-paclitaxel, or any of their components.
• Active or history of autoimmune disease with potential for relapse (e.g., SLE, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis) or high risk (e.g., organ transplant requiring immunosuppressive therapy). \*\*Exceptions allowed for\*\*:
  • Type I diabetes mellitus stabilized on fixed insulin regimen;
  • Autoimmune hypothyroidism on hormone replacement therapy only;
  • Skin conditions not requiring systemic therapy (e.g., eczema, rash involving \< 10% BSA, psoriasis without ocular symptoms).
• History of allogeneic organ or hematopoietic stem cell transplantation.
• Untreated acute/chronic active hepatitis B or hepatitis C infection. \*\*Exceptions\*\*:
  • HBV carriers or patients stabilized on antiviral therapy with HBV DNA ≤ 500 IU/mL or \< 2500 copies/mL are allowed.
  • Active hepatitis C defined as positive anti-HCV antibody with quantifiable HCV RNA above the lower limit of detection.
• Active bleeding or new thrombotic disease on therapeutic anticoagulation, or bleeding diathesis.
• Active tuberculosis.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation.

Lab values

• Uncontrolled concurrent illness, including but not limited to:
  • HIV positive;
  • Active or poorly controlled severe infection;
  • Severe or uncontrolled systemic disease (e.g., severe psychiatric/neurological disorders, epilepsy/dementia, unstable or uncompensated respiratory, cardiovascular, hepatic, or renal disease);
  • Unstable systemic disease such as diabetes (fasting glucose ≥ 10 mmol/L) or hypertension (systolic BP \> 150 mmHg or diastolic BP \> 90 mmHg).

Age

• History of invasive malignancy ≤ 5 years prior to informed consent, except adequately treated basal/squamous cell skin cancer or in situ cervical cancer.

Other

• Stage IV (metastatic) TNBC.
• Pregnant or lactating female patients.

• Voluntary participation and signed informed consent.
• Age ≥ 18 years, male or female.
• Histologically confirmed invasive breast carcinoma with documented ER-negative, PR-negative, and HER2-negative status, defined as:
  • ER and PR: nuclear staining \< 10% by IHC;
  • HER2: 0 or 1+ by IHC, or 2+ with negative FISH amplification.
  • Known PD-L1 status.
• Assessed by breast surgeon as eligible and planned for radical mastectomy.
• Clinical stage II-III per AJCC 8th edition and at least one measurable lesion per RECIST v1.1.
• No prior systemic therapy for the current disease, including surgery, radiotherapy, chemo/immunotherapy, etc.
• ECOG performance status 0-1.
• Adequate hematologic and organ function, as defined by:
  • Absolute neutrophil count ≥ 1.5 × 10⁹/L;
  • Platelet count ≥ 100 × 10⁹/L;
  • Hemoglobin ≥ 90 g/L;
  • Total bilirubin ≤ 1.5 × ULN;
  • AST, ALT, and ALP ≤ 2.5 × ULN;
  • Serum creatinine ≤ 1.5 × ULN or creatinine clearance (Cockcroft-Gault formula) ≥ 50 mL/min.
• Adequate cardiac function:
  • NYHA class \< 3;
  • Left ventricular ejection fraction (LVEF) ≥ 50%.
• Life expectancy ≥ 3 months.
• Contraceptive requirements:
  • \*\*Female patients\*\*: surgically sterile, postmenopausal, or agree to use at least one medically approved contraceptive measure (e.g., IUD, oral contraceptives, condoms) during and for 6 months after the treatment period; negative serum/urine pregnancy test within 7 days prior to enrollment; not lactating.
  • \*\*Male patients\*\*: agree to use at least one medically approved contraceptive measure (e.g., condom, abstinence) during and for 6 months after the treatment period.
• Willing and able to comply with study visits, procedures, prohibitions, and restrictions specified in the protocol.