A phase I study to assess the safety of adjuvant natural killer cell injection in combination with standard treatment in patients with radical pancreatectomy.

Abstract

e14534 Background: Adjuvant chemotherapy for six months is recommended for patients who have undergone radical pancreatectomy, regardless of stage. The objective of this study is to analyse the safety and efficacy of administration of autologous natural killer(NK) cells, which are known for their high safety and low toxicity, in combination with standard chemotherapy. Methods: We conducted a phase I study in three patients who had undergone radical (R0) pancreatectomy. The adjuvant chemotherapy regimen consisted of 1000 mg/m 2 gemcitabine administered weekly on days 1, 8, and 15 during a 28-day cycle, followed by a 2-weeks’ rest and 825 mg/m 2 capecitabine administered twice daily for 21 days within the same 28-day cycle, followed by a 7days’ rest. In each cycle of chemotherapy, 50 cc of blood is collected on the first day (D1), and 2x10 9 autologous NK cells, cultured for three weeks, are administered intravenously on the day after the completion of chemotherapy (D22). This process is repeated for all six planned cycles, resulting in a total of six doses. The primary endpoint of the study is to evaluate the safety of combining autologous NK cells with standard adjuvant chemotherapy, and the secondary endpoint is to assess clinical effectiveness, including disease-free survival. Results: Of the three patients enrolled, two patients completed chemotherapy and NK cell infusions and one patient received up to five cycles of chemotherapy and only four NK cell infusions. Grade 3 adverse events were hematological adverse events, including neutropenia, anemia and thrombocytopenia, which were considered to be directly related to chemotherapy. Immune cell activity assays were performed eight times: baseline on cycle 1 D1, then every cycle D1, at the end of treatment and 4 weeks after the end of treatment. No significant changes were observed with the NK cell administration. Conclusions: This study confirmed the safety of administering autologous NK cells to patients who underwent radical pancreatectomy in combination with standard chemotherapy. However, further follow-up is required to confirm the clinical effect of NK cell administration, and studies with larger numbers of patients are needed. Funding: The trial was funded by the Regenerative Medicine Acceleration Foundation (RMAF), project number HX23C0086. Clinical trial information: HX23C0086 .