Article Text

Download PDFPDF
181 INTRO-study: intraperitoneal infusion of allogeneic stem-cell derived natural killer cells in recurrent ovarian carcinoma patients
  1. Janneke Hoogstad-Van Evert1,
  2. Paul De Jonge2,
  3. Petra Zusterzeel3,
  4. Willemijn Hobo2,
  5. Anniek Van De Waart2,
  6. Lisanne Janssen2,
  7. Hanny Fredriks2,
  8. Maud Wuts2,
  9. Lynn Bosmans4,
  10. Ellen Spijkers4,
  11. Merlize Djojoatmo4,
  12. Veronica Castano Radriguez4,
  13. Ralph Maas2,
  14. Jolien Van Der Meer2,
  15. Anna De Goede5,
  16. Michel Schaap6,
  17. Ruud LM Bekkers3,
  18. Joop Jansen2,
  19. Nelleke Ottevanger7 and
  20. Harry Dolstra2
  1. 1Department of Gynecology, Amphia, Breda, The Netherlands
  2. 2Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
  3. 3Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
  4. 4Departement of Laboratory Medicine, Radboud UMC, Nijmegen, The Netherlands
  5. 5Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands
  6. 6Department of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands
  7. 7Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands


Introduction/Background Median 5 year overall survival for patients with epithelial ovarian cancer(EOC) is poor. New therapeutic options are needed. Allogeneic natural killer (NK)-cell therapy may be such an option. NK cells are tolerant to normal cells, but have killing potential against malignant cells. Our GMP compliant NK-cell product (RNK001) from umbilical cord blood derived hematopoietic stem and progenitor cells is active against ovarian cancer cells in vitro and in vivo.

Methodology The INTRO-study (NCT03539406) is a phase-I clinical trial evaluating the feasibility, safety and toxicity of intraperitoneal (IP) infusion of RNK001 combined with IL2 without or with lymphodepletion by Fludarabine/Cyclophosphamide (Flu/Cy). EOC patients with rising CA-125 at second recurrence were eligible.

Results Six patients without Flu/Cy and 1 patient with Flu/Cy were treated with RNK001. The infusion of RNK001 and IL2 through a IP port is feasible. There were two serious adverse events in different patients: a grade 3 (CTCAE III-IV) rise of liver enzymes, and a grade 3 ileus. After one week we detected 0.24 and 1.02% donor NK cells in the peritoneal fluid of two patients. In 5/7 patients, CA-125 serum levels decreased by 20–53% at day 14 after RNK001 from baseline. One patient had a partial response (according to RECIST) with a progression-free survival (PFS) of 9 months (median PFS of all patients was 3 months).

Conclusion We have shown the feasibility and safety of intraperitoneal infusion of in seven patients. We found a transient decline in CA-125 levels and one patient with a partial response and a PFS of 9 months. Flu/Cy in patients with second recurrence was not feasible due to refusal of the patients. We will continue clinical research with a phase 2 study investigating RNK001 intraperitoneal infusion combined with carboplatin paclitaxel.

Disclosures Authors have nothing to disclose.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.