This is a prospective, multicenter, non-randomized, open label light dose escalation phase I trial to evaluate the safety and preliminary efficacy of Padeliporfin vascular targeted photodynamic therapy (VTP) applied via endovascular fiber placement within a dilatation catheter, through the target artery(superior mesenteric artery (SMA), celiac artery (CA) or common hepatic artery (CHA)). The investigators will evaluate safety and preliminary efficacy of Padeliporfin VTP administered endovascularly using light dose escalation.

This is a prospective, multicenter, non-randomized, open label light dose escalation phase I trial to evaluate the safety and preliminary efficacy of Padeliporfin vascular targeted photodynamic therapy (VTP) applied via endovascular fiber placement within a dilatation catheter, through the the target artery(superior mesenteric artery (SMA), celiac artery (CA) or common hepatic artery (CHA)).The investigators will evaluate safety and preliminary efficacy of Padeliporfin VTP administered endovascularly using light dose escalation.

Study Intervention: Patients enrolled in the study will undergo endovascular VTP, using Padeliporfin (WST-11) activated via endovascular fiber placement through the target artery(superior mesenteric artery (SMA), celiac artery (CA) or common hepatic artery (CHA))., with intravenous administration of Padeliporfin at a fixed dose of 4 mg/kg of padeliporfin di-potassium, followed by total of 10 min illumination at 753 nm.

For light dose escalation (Part A), a 3+3 dose-escalation schema will be used. In a subsequent expansion phase (Part B), the optimal light dose as per light dose escalation, will be used in an additional cohort of patients to further evaluate preliminary efficacy.

Inclusion Criteria:

1Patient is 18 years of age and older 2. Patient is capable of giving written informed consent 3. Patients with a diagnosis of Stage III pancreatic ductal adenocarcinoma, cytologically or histologically confirmed per American Joint Committee on Cancer (AJCC) staging criteria 4. Patients have an unresectable tumor, evaluated as Stage III according to National Comprehensive Cancer Network (NCCN) guidelines resectability criteria, based on radiographic imaging or exploratory surgery as a locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) 5. Patients with LA PDAC located in the head/uncinate process of the pancreas 6. Patient with target artery solid tumor contact ˃180° for a total contact length up to 3cm, and with entire target artery internal diameter 5-10 mm. 7. All patients will be approved by a multi-disciplinary team (including medical oncologist, surgeon, interventional radiologist) as appropriate for endovascular VTP treatment. 8. Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors according to RECIST 1.1 9. ECOG performance status ≤ 1 10. Life expectancy at least 6 months 11. No evidence of metastatic disease by CT scan chest, abdomen and pelvis performed within 28 days prior to treatment 12. Adequate organ system function including:

a. Absolute neutrophil count (ANC) ≥1500/mm3 without the use of hemopoietic growth factors within the 7 days before VTP treatment b. Absolute white blood cell count ≥3.0*109/L c. Hemoglobin at least 10g/dL d. Platelet count ≥75,000/mm3 e. International normalized ratio (INR) <1.5 unless the patient is receiving anticoagulation therapy, in which case a therapeutic INR is acceptable. Anticoagulation therapy with low- molecular-weight heparin whether medically indicated, is permitted. f. Creatinine clearance ≥60 mL/min using Cockcroft-Gault equation g. Amylase and lipase <1.5xULN h. ALT/AST ≤2.5*ULN and total bilirubin ≤2*ULN (benign hereditary hyperbilirubinemias, e.g., Gilbert's syndrome, are permitted, those patients must have total bilirubin <3 mg/dL).

13. Patient may have received prior neoadjuvant systemic therapy (chemotherapy and/or immunotherapy) 14. Patient with no prior external beam radiation therapy to the pancreas 15. Patient with prior attempted surgical resection is permitted 16. No comorbidities which would preclude access to the target artery by endovascular catheterization 17. Male or nonpregnant and nonlactating female aged ≥18 years

• Women of child-bearing potential (i.e., fertile, following menarche, and until becoming postmenopausal unless permanently sterile; permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) must test negative for pregnancy at the time of screening on the basis of a urine or serum pregnancy test.
• Postmenopausal women are defined as those who have had an absence of menstruation for at least 2 years.
• Female subjects of reproductive potential must agree to use two effective methods of birth control during the study and for 1 month after the last dose of study medication.
• Male subjects must agree to use condoms during the study and for 90 days after the last dose within the 7 days before VTP treatment of study medication.

Participant exclusion criteria

1. Metastatic (stage IV) disease
2. SMA originated not from aorta
3. Any anatomical variant or vascular abnormality that precludes safe placement of the balloon and device assembly in the target artery in the discretion of the principle investigator.
4. Hemodynamically significant moderate to severe atherosclerotic flow limiting changes of target vessel wall
5. Hemodynamically significant stenosis of the CA
6. Previous radiotherapy treatment for pancreatic cancer
7. Cystic component >= 25% the total volume of the tumor
8. Moderate to severe clinical ascites not controlled by medication detected by CT, ultrasound (US) or MRI;
9. Known additional malignancy that is progressing and/or requires active treatment.
10. Cardiac function: history of congestive heart failure or recent (within 6 months) myocardial infarction or ischemic event
11. Unable to receive or previously intolerant of moderate and/or deep sedation
12. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, and participate in the study or that is likely to interfere with the interpretation of the results
13. Unwilling or unable to comply with study procedures and/or study visits
14. Receipt of prior definitive resection for pancreatic cancer
15. Pregnant and/or nursing
16. Active infection
17. Known hypersensitivity to iodine contrast
18. Receipt of concurrent investigational therapy or within 30 days of protocol initiation
19. Any other medical or psychiatric comorbidities, including decompensated heart failure, unstable angina or coronary artery disease or severe pulmonary disease, that, in the opinion of the study investigator, would make the patient a poor candidate for the study. Systemic chemotherapy treatment within at least 14 days prior to planned VTP. Preferred wash out period is 30 days.

21. VEGF-targeted therapy within 2 months prior to planned VTP treatment 22. Prohibited medication that could not be adjusted or discontinued prior to study treatment (See Section 16 for instructions) 23. Patients with photosensitive skin diseases or porphyria.