Protein-Matched ADC or PDC Umbrella Trial in Advanced Pancreatic and Breast Cancer

To evaluate the clinical efficacy (objective response rate, ORR) of mass spectrometry-based absolute quantification-guided selection and matching of ADC/PDC therapy in patients with locally advanced or metastatic pancreatic cancer/breast cancer, and to explore a quantitative threshold-based stratification strategy for identifying a "hidden benefit population

Inclusion Criteria: 1. Male or female patients aged ≥18 years and ≤75 years at the time of informed consent. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 3. Life expectancy of ≥3 months, as assessed by the investigator. 4. Histologically confirmed recurrent (unresectable) or metastatic advanced pancreatic cancer or breast cancer. 5. Radiographic or objective evidence of disease progression during or following the last systemic therapy administered prior to the first dose of study treatment. 6. Documented failure of standard-of-care therapy in the recurrent/metastatic setting, with receipt of at least 2 prior lines of chemotherapy. If disease recurrence occurs within 6 months after completion of (neo)adjuvant chemotherapy, the adjuvant chemotherapy regimen shall be counted as 1 line of prior chemotherapy. Additionally: For patients with hormone receptor-positive (estrogen receptor \[ER\]-positive and/or progesterone receptor \[PR\]-positive) and HER2-negative tumors: progression after at least 1 line of endocrine therapy, with the investigator's determination that the patient is unlikely to benefit from further endocrine therapy. Primary endocrine resistance in the adjuvant setting shall be counted as 1 line (disease recurrence within 24 months after completion of adjuvant endocrine therapy is considered 1 line). Prior treatment with CDK4/6 inhibitors is permitted. For patients with HER2-positive advanced breast cancer: receipt of at least 2 prior lines of anti-HER2 therapy. 7. At least 1 extracranial measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 8. Adequate organ and bone marrow function, as demonstrated by the following laboratory values obtained within 14 days prior to the first dose of study treatment: 1. Hemoglobin ≥90 g/L (without transfusion within 14 days prior to screening). 2. Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L. 3. Platelet count ≥90 × 10⁹/L. 4. Total bilirubin ≤1.5 × upper limit of normal (ULN). 5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN; if hepatic metastases are present, ALT and AST ≤5 × ULN. 6. Serum creatinine ≤1.5 × ULN, or creatinine clearance ≥60 mL/min as calculated by the Cockcroft-Gault formula. 7. International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN. 8. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiography or multigated acquisition (MUGA) scan; QTcF \10 mg/day prednisone or equivalent dose of other corticosteroids). Nasal spray or inhaled corticosteroids are excluded from this criterion. 10. Any active autoimmune disease or history of autoimmune disease with potential for relapse. Patients with skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia), well-controlled type 1 diabetes mellitus on insulin therapy, or asthma that has completely resolved since childhood and requires no intervention in adulthood may be enrolled. Patients with asthma requiring bronchodilator therapy are not eligible. 11. Uncontrolled infection requiring intravenous antibiotics, antiviral agents, or antifungal agents. 12. Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, active hepatitis B (HBsAg-positive with HBV DNA ≥500 IU/mL), or active hepatitis C infection. Among patients who are hepatitis C antibody-positive, only those with negative HCV RNA by polymerase chain reaction (PCR) are eligible for enrollment. 13. Unresolved toxicity from prior anti-cancer therapy, defined as toxicity not resolved to Grade ≤1 or baseline (excluding alopecia). Patients with chronic, stable Grade 2 toxicity that the investigator considers related to prior anti-cancer therapy (defined as no worsening to Grade ≥2 for at least 3 months prior to enrollment and manageable with standard treatment) may be enrolled (e.g., chemotherapy-induced neuropathy, fatigue). Residual toxicity from prior immune-oncology (IO) therapy: Grade 1 or Grade 2 endocrinopathies, which may include: (a) hypothyroidism/hyperthyroidism; (b) type 1 diabetes mellitus; (c) hyperglycemia; (d) adrenal insufficiency; (e) adrenalitis; (f) skin depigmentation (vitiligo). 14. Imaging evidence of tumor invasion into major blood vessels, or, in the investigator's judgment, a very high likelihood of tumor invasion into major blood vessels during treatment that could result in fatal hemorrhage. 15. Major surgical procedure, severe traumatic injury, fracture, or ulcer within 4 weeks prior to the first dose of study treatment. 16. Pregnant or breastfeeding women; women of childbearing potential who are unwilling or unable to use highly effective contraceptive measures. 17. Any other condition that, in the investigator's judgment, may interfere with the conduct of the study or the interpretation of study results.