DKN-01 Treatment of Gastric and GE Junction Cancers
by Dr. C.H. Weaver M.D. 7/2020
The FDA has granted an Orphan Drug Designation to DKN-01 for the treatment of patients with gastric and gastroesophageal junction (GEJ) cancer, according to a press release from developer Leap Therapeutics. (1)
DKN-01 is a novel humanized monoclonal antibody that targets the DKK1 protein, which modulates Wnt/beta-catenin signaling. DKK1 is known to play a role in cancer cell signaling and mediating an immunosuppressive cancer microenvironment by boosting the activity of myeloid-derived suppressor cells and down regulating natural killer ligands on cancer cells which may prevent cancer cell growth.
The KEYNOTE-731 clinical trial is exploring the use of DKN-01 alone and in combination with paclitaxel chemotherapy or Keytruda (pembrolizumab) immunotherapy in patients with advanced esophagogastric cancers who have been previously treated with standard therapies
The combination of DKN-01 plus a PD-1 checkpoint inhibitor in patients with advanced or recurrent gastroesophageal adenocarcinoma who had no prior exposure to PD-1/PD-L1 checkpoint blockade has anti-cancer activity in patients with a high tumor DKK1 expression. (2,3) The objective response rate among the 10 evaluable patients with high DKK1 expression on cancer cells was 50% and the disease control rate in these patients was 80%. Patients with low DKK1 expression did not appear to derive benefit from treatment.
[doi](https://en.wikipedia.org/wiki/Doi_(identifier%29 "Doi (identifier)"):10.1158/0008-5472.CAN-08-4135
Klempner SJ, Bendell JC, Villaflor VM, et al. DKN-01 in combination with pembrolizumab in patients with advanced gastroesophageal adenocarcinoma (GEA): Tumoral DKK1 expression as a predictor of response and survival. J Clin Oncol. 2020;38(suppl 4):357.
Leap Therapeutics Presents Updated Data at the ASCO 2020 Gastrointestinal Cancers Symposium (ASCO GI) Global Meeting | Leap Therapeutics, Inc.
- Improved clinical outcomes in advanced gastric/gastroesophageal junction cancer patients with DKK1-high tumors when treated with DKN-01 and anti PD-1 therapy - Tumoral DKK1 levels will be used to prospectively identify patients in subsequent studies in new collaboration with BeiGene - Radiomic