Article Text

Download PDFPDF

76 Patients (PTS) with recurrent gynecologic cancer whose tumors have activating wnt pathway mutations respond better to DKN-01, a DICKKOPF-1 (DKK1) inhibitor
  1. R Arend1,
  2. C Castro2,
  3. U Matulonis3,
  4. E Hamilton4,
  5. C Gunderson5,
  6. K LyBarger6,
  7. H Goodman7,
  8. L Duska8,
  9. H Mahdi9,
  10. A ElNaggar10,
  11. M Kagey11,
  12. L Barroilhet12,
  13. W Bradley13,
  14. J Sachdev14,
  15. D O’Malley15,
  16. C Sirard16 and
  17. M Birrer1
  1. 1University of Alabama at Birmingham, Gynecologic Oncology, Birmingham, USA
  2. 2Massachusetts General Hospital, Hematology/Oncology, Boston, USA
  3. 3Dana Farber Cancer Institute, Gynecologic Oncology, Boston, USA
  4. 4Sarah Cannon Research Institute/Tennessee Oncology, Breast and Gynecologic Cancer Research Program, Nashville, USA
  5. 5The University of Oklahoma Health Sciences Center, Gynecologic Oncology, Oklahoma City, USA
  6. 6Sarah Cannon Research Institute at HCA Midwest, Gynecologic Oncology, Kansas City, USA
  7. 7Florida Cancer Specialists, Gynecologic Oncology, West Palm Beach, USA
  8. 8University of Virginia Health System, Gynecologic Oncology, Charlottesville, USA
  9. 9Cleveland Clinic, Gynecologic Oncology, Cleveland, USA
  10. 10West Cancer Clinic, Gynecologic Oncology, Memphis, USA
  11. 11Leap Therapeutics- Inc., Research, Cambridge, USA
  12. 12University of Wisconsin Hospitals and Clinics, Gynecologic Oncology, Madison, USA
  13. 13Froedtert and Medical College of Wisconsin, Gynecology/Oncology, Milwaukee, USA
  14. 14HonorHealth Research Institute, Hematology/Oncology, Scottsdale, USA
  15. 15Ohio State University, Gynecologic Oncology, Columbus, USA
  16. 16Leap Therapeutics- Inc., Clinical Research, Cambridge, USA


Objectives Wnt/β-catenin signaling is frequently dysregulated in gynecologic malignancies. CTNNB1, APC and RNF43 mutations cause pathway activation; CTNNB1 stabilizing mutations lead to elevated DKK1 expression which promotes an immune suppressive tumor microenvironment. Neutralization by DKN-01 (D), a mAb against DKK1, is being tested in a phase 2 basket study.

Methods Eligibility included recurrent endometrial cancer (EC) or platinum resistant/refractory ovarian cancer (OC) enriched (∼50%) for Wnt signaling-related genetic alterations. Subgroup analysis was done in pts with genetic alterations associated with activation of Wnt/β-catenin signaling (CTNNB1, APC or RNF43). Pts were assigned (MD discretion) to receive D (300 mg on Days 1 & 15) or D + paclitaxel (P) (80 mg/m2 on Days 1, 8 and 15) of a 28-day cycle. Primary endpoint is ORR; exploratory endpoints: DKK1 expression (serum/plasma/tumor), tumor genetics, infiltrating immune cells, and β-catenin IHC.

Results 80 pts are enrolled: D (n=33, 19 EC, 14 OC); D + P (n=47; 28 EC, 19 OC); 18 pts with CTNNB1 (n=13), APC (n=2), RNF43 (n=2), or CTNNB1 + RNF43 (n=1). 54 pts evaluable for response (table 1). D and D + P were safe and well tolerated with no additive toxicities. The trial is ongoing; updated safety, efficacy and correlative work are pending.

Abstract 76 Table 1

Conclusions D and D + P have activity in pts with recurrent gyn cancers; the role of Wnt/β-catenin pathway activation as a potential biomarker for response is currently under study. Clinical trial information: NCT03395080.

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.