Re-challenge Immunotherapy With Cromolyn, TQB2102, and Panpulimab in Immune-Refractory Triple Negative Breast Cancer

Inclusion Criteria:

1. Age: Female, ≥18 years old and ≤70 years old.
2. Diagnosis: Histologically confirmed invasive triple-negative breast cancer (defined as: ER-negative by IHC with \<1% positive tumor cells; PR-negative with \<1% positive tumor cells; HER2 0-1+ or HER2 2+ with confirmed negative FISH/CISH without amplification).
3. Prior Treatment: Recurrent or metastatic refractory breast cancer with disease progression after prior immunotherapy.
4. Measurable Disease: At least one measurable lesion per RECIST v1.1 (≥20 mm by conventional CT or ≥10 mm by spiral CT; lesion must not have been previously irradiated).
5. Organ Function: Adequate organ function as follows:

   1. Blood Counts: Hemoglobin ≥90 g/L (no transfusion within 14 days); absolute neutrophil count ≥1.5×10⁹/L; platelets ≥75×10⁹/L.
   2. Blood Chemistry: Total bilirubin ≤1.5×ULN; ALT and AST ≤3×ULN (≤5×ULN if liver metastases are present); serum creatinine ≤1×ULN; creatinine clearance \>50 mL/min (Cockcroft-Gault formula).
6. Treatment-Free Interval: No radiotherapy, endocrine therapy, molecular targeted therapy, or major surgery within 3 weeks prior to study entry; recovery from prior treatment-related toxicities (surgical wounds fully healed if applicable); absence of peripheral neuropathy or only grade I peripheral neuropathy.
7. Performance Status: ECOG performance status ≤1, and life expectancy ≥3 months.
8. Contraception: Women of childbearing potential must agree to use medically approved contraception during the study treatment period and for at least 3 months after the last dose of the study drug.
9. Consent: Voluntary participation with signed informed consent, good compliance, and willingness to cooperate with follow-up.

Exclusion Criteria:

1. Prior Radiotherapy: Receipt of radiotherapy within 3 weeks before treatment initiation (except for palliative reasons).
2. CNS Metastases: Known history or presence of central nervous system (CNS) metastases at screening. Patients with clinical suspicion of CNS metastases must undergo contrast-enhanced CT or MRI within 28 days prior to the first dose to rule out CNS involvement.
3. Cardiac Disease: History of clinically significant or uncontrolled cardiac conditions, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.
4. Persistent Toxicity: Ongoing ≥ Grade 1 adverse reactions from previous treatments, except for alopecia or conditions deemed acceptable by the investigator. Such exceptions must be clearly documented in the investigator's notes.
5. Recent Major Surgery: Undergone major surgery (excluding minor outpatient procedures such as vascular access placement) within 3 weeks before the first cycle of study treatment.
6. Pregnancy or Lactation: Patients who are pregnant or breastfeeding.
7. Other Malignancies: History of other malignant tumors within the past 5 years (except cured basal cell carcinoma of the skin or carcinoma in situ of the cervix).
8. Impaired Drug Absorption: Conditions affecting oral drug intake and absorption, such as dysphagia, chronic diarrhea, or intestinal obstruction.
9. Uncontrolled Effusions: Uncontrolled third-space effusions (e.g., significant pleural or ascitic fluid) not manageable by drainage or other methods.
10. Non-Healing Conditions: Long-term non-healing wounds or incompletely healed fractures.
11. Active Viral Hepatitis: Active HBV or HCV infection (HBV-DNA ≥ 500 IU/mL) or chronic hepatitis with abnormal liver function.
12. Allergic History: Known allergy or hypersensitivity to any component of the study regimen, or history of hypersensitivity to other monoclonal antibodies.
13. Eosinophilia/Mastocytosis: Patients with eosinophilia or mastocytosis.
14. Steroid Use: Chronic use of oral corticosteroids. Occasional past use requires a 4-week washout period before enrollment.
15. Prior Use of Specific Therapies: Previous treatment with PD-1/TGF-β bispecific antibody, PD-1/CTLA-4 bispecific antibody, PD-1/VEGF bispecific antibody, or anti-HER2 dual-epitope ADC; or use of ADC agents in ≥2 prior lines of therapy.