A Dose-Finding Phase I Followed by a Phase II Study to Evaluate the Safety and Efficacy of Allogeneic NK-cell Combined With Chemotherapy in Patients With PDA or Cholangiocarcinoma After Surgery
This is a phase I/II study which intends to characterize the safety, tolerability, and preliminary efficacy of Allogeneic Magicell-NK infusion in PDA or cholangiocarcinoma patients after surgery. Subjects will receive a total of 6 intravenous (IV) infusions of the IP on the 11th day of each chemotherapy cycle. A total of 6 cycles of IP infusions are planned. The phase I part of the study is a first-in-human phase I trial of Allogeneic Magicell-NK and is therefore designed in an open-label, dose-escalation manner. A standard 3+3 design will be employed to assess the safety profile of Allogeneic Magicell-NK and to determine the MTD/MFD. Two dose cohorts are planned: the starting dose is 10 × 10\^8 cells (Cohort 1), and escalates to 20 × 10\^8 cells (Cohort 2). The phase II part of the study is designed as an open-label, two-arm, randomized clinical trial comparing the combination of SLOG and Allogeneic Magicell-NK with SLOG alone when used as adjuvant therapy following resection for PDA or Cholangiocarcinoma. Approximately 30 subjects will be randomized at a 2:1 ratio between the two arms: Arm 1: SLOG and Allogeneic Magicell-NK (20 subjects); Arm 2: SLOG alone (10 subjects). Subjects will then receive 12 weeks of SLOG chemotherapy with or without Allogeneic Magicell-NK infusion.
• 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.