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 \<470 ms for female patients.
9. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive measures from the start of screening through 7 months after the last dose of study treatment, and must agree not to breastfeed. A negative serum pregnancy test is required within 7 days prior to the first dose of study treatment.
10. Voluntary written informed consent signed prior to any study-specific procedures, with the expectation of good compliance and willingness to adhere to all protocol-specified study requirements.
Exclusion Criteria:
1. Known history of severe hypersensitivity to the investigational drug substance, any excipients contained in the study drug formulation, or other monoclonal antibodies/peptides.
2. Participation in any other interventional clinical trial (excluding observational studies) within 4 weeks (or 5 half-lives of the investigational product, whichever is shorter) prior to the first dose of study treatment. Receipt of any of the following within the specified time windows prior to the first dose of study treatment:
oSurgery (major cancer-directed surgery), radiotherapy, chemotherapy, biological therapy, or participation in another interventional clinical study within 3 weeks.
oEndocrine therapy, immunotherapy, molecularly targeted therapy, or anti-cancer traditional Chinese medicine within 2 weeks.
3. Leptomeningeal metastases or active brain parenchymal metastases. Patients with clinically stable brain parenchymal metastases may be eligible, including those with asymptomatic brain metastases that have not received prior local therapy; or patients who have previously received treatment for CNS metastases (radiotherapy or surgery), provided that imaging-confirmed disease stability has been maintained for at least 4 weeks and symptomatic treatment (including corticosteroids and mannitol) has been discontinued for more than 2 weeks.
4. Presence of or history of other malignancies, with the following exceptions: cured basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, papillary thyroid carcinoma, ductal carcinoma in situ of the breast, or any other malignancy with disease-free survival exceeding 3 years.
5. Uncontrolled concurrent illness, including but not limited to: persistent or active infection, uncontrolled or clinically significant cardiovascular disease, severe chronic gastrointestinal disease associated with diarrhea, or any psychiatric illness or social situation that, in the investigator's judgment, would limit compliance with study requirements, significantly increase the risk of adverse events, or impair the ability to provide written informed consent.
6. Uncontrolled or clinically significant cardiovascular disease, including any of the following:
1. History of myocardial infarction or symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] Class II-IV) within 6 months prior to enrollment. Patients with troponin levels above the upper limit of normal (ULN) at screening, as defined by the manufacturer, in the absence of any myocardial infarction-related symptoms, must undergo cardiology consultation prior to enrollment to rule out myocardial infarction.
2. Uncontrolled hypertension.
3. Uncontrolled and/or clinically significant cardiac arrhythmias.
4. QT interval corrected by the Fredericia method (QTcF) \>470 ms for female patients, based on the mean of three 12-lead electrocardiogram (ECG) results obtained during the screening period.
7. History of steroid-treated (non-infectious) interstitial lung disease (ILD)/pneumonitis, current ILD/pneumonitis, or suspected ILD/pneumonitis on screening imaging that cannot be ruled out.
8. Clinically significant pulmonary comorbidities, including but not limited to: any underlying pulmonary disease (i.e., pulmonary embolism within 3 months prior to study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, significant pleural effusion, etc.); any autoimmune, connective tissue, or inflammatory disease with pulmonary involvement (i.e., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.); and/or prior pneumonectomy (completed).
9. Use of immunosuppressive agents or systemic corticosteroids for immunosuppressive purposes within 2 weeks prior to the first dose of study treatment (dose \>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.
