Pancreatic Carcinoma Stage II、Cholangiocarcinoma Resectable

主要目的： Dose-finding Phase I Part ●To assess the clinical safety/tolerability profile of escalating doses of Allogeneic Magicell-NK in PDA or cholangiocarcinoma patients post resection ●To assess the dose limiting toxicity (DLT) of Allogeneic Magicell-NK ●To determine the MTD/MFD of Allogeneic Magicell-NK Main Phase II part ●To evaluate the efficacy of Allogeneic Magicell-NK

溶液劑

Allogeneic NK cell

18A

100ML

Phase 1 Dose Exploration Trial Part

● Assess safety parameters (treatment-induced adverse events [TEAE], laboratory test values, body weight, vital signs, dose interruption/discontinuation)

● Determine the DLT, MTD/MFD for future trials and recommend the final dose

Phase 2 Trial Part

● Disease-free survival (DFS)

Inclusion Criteria:

Dated and signed informed consent
Either sex, aged older than 18 years old (inclusive) at date of consent
Subject with a macroscopic resection of the primary tumor and residual primary tumor that satisfies all of the items below according to the Union for International Cancer Control (UICC) histopathologic staging system:

At or before the surgery, stage II or stage III where resection included the celiac artery
Local residual tumor classified as R0 or R1
Cytologic examination negative upon intraoperative peritoneal lavage
Histologically confirmed PDA or cholangiocarcinoma
Received curative resection within 12 weeks prior to screening visit and will receive adjuvant SLOG chemotherapy Note: Subjects with cancer who had undergone surgery with or without prior neo-adjuvant therapy will be recruited.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
Subject with adequate hematology function at Visit 1:

Total white blood cell (WBC) ≥ 3,000 cells/mm3
Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
Platelets ≥ 100,000 counts/mm3
Hemoglobin ≥ 9 g/dL
International normalized ratio (INR) of prothrombin time within normal range Note: Re-test for eligibility is allowed during the screening period.
Subject with adequate hepatic and renal function at Visit 1:

Serum creatinine ≤ 1.5× Upper Limit of Normal (ULN)
Blood urea nitrogen (BUN) ≤ 1.5× ULN
Total bilirubin ≤ 1.5× ULN
Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5× ULN
Alkaline phosphatase (ALP) ≤ 5× ULN
Albumin ≥ 3.0 g/dL Note: Re-test for eligibility is allowed during the screening period.
Negative response in human immunodeficiency virus (HIV) and treponema pallidum (rapid plasma reagin [RPR]/venereal disease research laboratory [VDRL] and treponema pallidum hemagglutination [TPHA])
Subject confirmed with past cytomegalovirus (CMV) infection in terms of having positive CMV immunoglobin G (CMV IgG)
Subject with childbearing potential must agree to use at least two contraceptive precautions, one of which must be a condom or other adequate barrier method, from

signing informed consent until 28 days after the last dose of investigational product (IP) administration
initiation of oxaliplatin treatment until at least 15 months (female) or 12 months (male) following the last dose
initiation of gemcitabine treatment until at least 6 months (female) or 3 months (male) following the last dose
Agree to be in compliance with clinical protocol-planned treatment Note: Anti-virus treatment is allowed if active hepatitis B is presented.

Exclusion Criteria:

Received any other investigational, anti-neoplastic medications, or immune cell therapy within 28 days prior to screening visit
Any prior history of malignant neoplasm, except:

Non-invasive, non-melanomatous skin cancer (including squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ), curatively treated with cryosurgery or surgical excision only
Other primary malignant neoplasm diagnosed as disease free for more than 5 years
Immunocompromized, currently under immunosuppressive treatment for autoimmune disease, or have received systemic steroid of equivalent dosage higher than prednisolone 30 mg/day for more than 7 days within 14 days prior to Day 1
With known metastases
With ongoing acute diseases, or serious medical conditions within the past 2 years prior to screening, such as cardiovascular (e.g., New York Heart Association grade III or IV), hepatic (e.g., Child-Pugh Class C), psychiatric condition (e.g., alcoholism, drug abuse), medical history, physical findings, or laboratory abnormality that in the investigators' opinion could interfere with the results of the trial or adversely affect the safety of the subject
Hypercoagulable state that may lead to clinically apparent thrombosis
With known hypersensitivity to aminoglycoside (e.g., streptomycin, gentamicin) or bacitracin
With known hypersensitivity to any of the components of Allogeneic Magicell-NK, including human serum albumin
With known hypersensitivity to any of the components of S 1, leucovorin, oxaliplatin, or gemcitabine
With any contraindication to S-1, leucovorin, oxaliplatin, or gemcitabine, including:

- Severe myelosuppression or myelosuppression that probably exacerbates

With symptomatic CMV disease
With any history of diagnosed or suspected cardiac arrhythmia or QT interval prolongation
Male subject with a corrected QT interval (QTc) ≥ 450 ms and female subject with a QTc ≥ 470 ms as determined by electrocardiogram (ECG) examination at screening.
Received any drugs associated with QT prolongation within 28 days prior to the Screening Visit (refer to Appendix 3. Drugs Associated with QT Prolongation, including but not limited to the drug listed therein)
Received brivudine or its analogs (e.g., sorivudine) or any live vaccines within 28 days prior to the Screening Visit
Female subject who is lactating or has positive serum or urine pregnancy test at screening