FDA Grants DKN-01 Orphan Drug Status for Gastric/GEJ Cancer

The FDA has granted an Orphan Drug designation to DKN-01 for the treatment of patients with gastric cancer or gastroesophageal junction cancer.

The FDA has granted an Orphan Drug designation to DKN-01 for the treatment of patients with gastric cancer or gastroesophageal junction (GEJ) cancer, according to Leap Therapeutics, Inc., the manufacturer of the DKK1 inhibitor.1

"Orphan Drug Designation for DKN-01 in gastric and gastroesophageal junction cancer is another significant milestone in our DKN-01 development program and underscores the need for new treatment options for these indications," said Douglas E. Onsi, president and chief executive officer of Leap. "We believe DKN-01 has the potential to be an important new therapy for this patient population that remains an area of high unmet medical need."

Data from the phase 1/2 P102/KEYNOTE-731 trial of DKN-01 were presented at the 2020 ASCO GI annual meeting. The study explored DKN-01 as a monotherapy and in combination regimens in previously treated patients with advanced esophagogastric cancer.2 Specifically, patients received single-agent DKN-01, DKN-01 combined with paclitaxel, or DKN-01 combined with pembrolizumab (Keytruda).

In the study, DKN-01 plus pembrolizumab showed positive outcomes in patients with gastric/GEJ cancer whose tumors were DKK1-high and who had not had prior treatment with a PD-1/PD-L1 inhibitor. Among 10 evaluable patients in this group, the median progression-free survival (PFS) was over 22 weeks, the median overall survival (OS) was almost 32 weeks, the objective response rate (ORR) was 50%, and the disease control rate was 80%. Among 15 evaluable patients with DKK1-low tumors, the median PFS was about 6 weeks, the median OS was over 17 weeks, and the disease control rate was 20%.

In the study, there was no correlation between PD-L1 level as measure by combined positive scores (CPS) and the efficacy of the combination regimen of DKN-01 plus pembrolizumab. Multivariate analysis did, however, show that a high level of DKK1 correlated with longer PFS independent of PD-L1 CPS level.

According to Leap Therapeutics, “DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the DKK1 protein, a modulator of Wnt/Beta-catenin signaling, a signaling pathway frequently implicated in tumorigenesis and suppressing the immune system.DKK1 has an important role in tumor cell signaling and in mediating an immuno-suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK ligands on tumor cells.”

Overall, phase 1/2 and phase 2 clinical trials of DKN-01 are ongoing across multiple tumor types, including gastroesophageal, gynecologic, hepatobiliary, and prostate cancers.One specific trial of note is exploring DKN-01 plus the PD-1 inhibitor tislelizumab in patients with gastric/GEJ cancer. Patient dosing is expected to start soon.

The FDA Office of Orphan Products Development (OOPD) facilitates the development and review of treatments that show potential to improve treatment for patients with rare diseases or conditions. In this line, the OOPD grants an Orphan Drug designation to drugs and biologics that are being developed for the treatment, diagnosis, or prevention of rare diseases/disorders, which the OOPD defines as those affected fewer than 200,000 people in the United States


  1. Leap Therapeutics Announces Orphan Drug Designation of DKN-01 for the Treatment of Gastric and Gastroesophageal Junction Cancer. Accessed June 12, 2020. https://bit.ly/2AlIYJ7. Accessed June 12, 2020.
  2. Leap Therapeutics Presents Updated Data at the ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) Global Meeting. Posted January 23, 2020. https://bit.ly/2N4woRf. Accessed June 12, 2020.