Intraperitoneal infusion of stem cell-derived natural killer cells in recurrent epithelial ovarian cancer patients: Results of the phase 1 INTRO-01 trial

INTRODUCTION: Epithelial ovarian cancer (EOC) patients exhibit a poor 5-year overall survival rate of approximately 40 %, underscoring the urgent need for innovative therapies. Allogeneic natural killer (NK) cell therapy presents a promising and safe therapeutic option, given its ability to discriminate between normal and malignant cells with potent cytotoxic effects against malignant cells. METHODS: We present the first-in-human study exploiting the safety of the NK cell product designated RNK001, derived ex vivo from umbilical cord blood-derived hematopoietic stem and progenitor cells. This phase 1 INTRO-01 trial (NCT03539406) was initiated to assess the feasibility, safety, and toxicity of intraperitoneal (IP) infusion of RNK001 in EOC patients exhibiting elevated CA125 levels at the second recurrence. RNK001 infusion was supported by IP IL-2 in six patients, and was preceded in one patient by lymphodepleting chemotherapy with cyclophosphamide/fludarabine. RESULTS: NK cells and was well tolerated, with neither evidence of graft-versus-host disease nor cytokine release syndrome. One patient experienced a grade 3 transient elevation in liver enzymes, another patient exhibited grade 3 ileus caused by disease progression. Notably, five out seven patients demonstrated a reduction in CA125 serum levels of 20-53 % at 14 days post-infusion. Furthermore, one patient achieved a clinical and biochemical response with radiological stable disease and a progression-free survival of 9 months. CONCLUSION: These findings suggest that intraperitoneal RNK001-based immunotherapy can be safely administered to recurrent EOC patients without inducing severe toxicity, while clinical and biochemical responses warrant further development.