Study summary
Study design:
This is a single-arm, open-label, dose-escalation and dose-expansion clinical study to evaluate the safety and efficacy of multiple doses of SapDM275 tumor vaccine injection in combination with the AG regimen for the treatment of patients with metastatic pancreatic cancer who have not received prior systemic anti-cancer therapy and are planned to receive AG as first-line treatment.
Treatment must be initiated within 7 days after enrollment. Patients will receive intramuscular injections of SapDM275 tumor vaccine combined with AG regimen until the occurrence of any of the following: disease progression, intolerable toxicity, death (whichever occurs first), the investigator's assessment that the subject is no longer suitable for further treatment, or withdrawal of consent by the subject.
Eligibility
Inclusion Criteria:
1. Age ≥18 years;
2. Histologically or cytologically confirmed unresectable metastatic pancreatic cancer;
3. No prior systemic anti-tumor therapy for metastatic pancreatic cancer. Neoadjuvant or adjuvant therapy is permitted, provided no disease progression occurred within 6 months after the last administration;
4. At least one measurable lesion according to RECIST v1.1 criteria;
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1;
6. Expected survival ≥6 months and ability to receive tumor vaccine and AG regimen treatment;
7. Adequate organ and bone marrow function at screening, defined as follows:
Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L without granulocyte colony-stimulating factor support; Platelet count (PLT) ≥100 × 10⁹/L without transfusion; Hemoglobin ≥90 g/L; Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥50 mL/min (calculated using the Cockcroft-Gault equation); Total bilirubin (BIL) ≤1.5 × ULN; Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) ≤2.5 × ULN (≤5 × ULN for patients with liver metastases); Coagulation parameters: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN; international normalized ratio (INR) ≤1.5 × ULN.
8. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan;
9. Willingness and ability to provide written informed consent and comply with protocol-specified visits and procedures;
10. Fertile patients (male and female) must agree to use reliable contraception (hormonal, barrier methods, or abstinence) during the study.
Exclusion Criteria:
1. Active or prior autoimmune disease, immunodeficiency, or primary immunodeficiency (including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis). Exceptions include:
Autoimmune hypothyroidism controlled with thyroid hormone replacement therapy; Well-controlled type 1 diabetes managed with insulin; Eczema, psoriasis, neurodermatitis, or vitiligo limited to skin involvement, with rash \<10% of body surface area, stable at baseline, requiring only low-potency topical corticosteroids, and no acute exacerbations within the past 12 months.
2. Receipt of systemic immunosuppressive drugs (including but not limited to glucocorticoids, cyclophosphamide, azathioprine, methotrexate, thalidomide, anti-TNF agents, etc.) within 2 weeks before initiation of study treatment, or anticipated need during the study, except in the following cases:
Short-term, low-dose systemic immunosuppression or a single pulse dose (e.g., glucocorticoids for 48 hours due to contrast allergy); Use of mineralocorticoids (e.g., fludrocortisone), inhaled corticosteroids, or low-dose corticosteroids (≤10 mg/day prednisone or equivalent) for chronic obstructive pulmonary disease/asthma, or low-dose corticosteroids for orthostatic hypotension/adrenal insufficiency.
3. History of other malignancies within 5 years prior to screening, except for cancers with negligible risk of metastasis or death (5-year recurrence-free survival \>90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ, or stage I endometrial cancer.
4. Severe cardiovascular, cerebrovascular, gastrointestinal, or hepatic disease, including:
Significant cardiovascular disease within 3 months prior to treatment (e.g., New York Heart Association \[NYHA\] Class III or IV heart failure, myocardial infarction, or cerebrovascular accident), unstable arrhythmias, or unstable angina; Severe colon or rectal disease, or postoperative complications resulting in grade ≥2 diarrhea, intestinal obstruction, or incomplete obstruction; Clinically significant liver disease, including active viral hepatitis, alcoholic hepatitis or other hepatitis, cirrhosis, hereditary liver disease, or investigator-assessed current alcohol abuse.
5. Active infections requiring treatment, including active HBV or HCV infection; known HIV infection or history of AIDS; active tuberculosis.
6. Toxicities from prior anti-tumor therapies not resolved to grade ≤2 per NCI-CTCAE v5.0 (or higher version) or baseline, except for alopecia and skin hyperpigmentation (any grade allowed).
7. Receipt of a live vaccine within 28 days prior to the first study treatment or planned receipt of a live vaccine during the study.
8. Positive serum pregnancy test or lactating women.
9. History of severe hypersensitivity to biologic products.
10. Any other condition that, in the opinion of the investigator, renders the subject unsuitable for study participation.