Leap Therapeutics has enrolled the first patient in Part C of the ongoing DisTinGuish Phase II clinical trial of its antibody DKN-01, along with tislelizumab, for gastric or gastroesophageal junction cancer (G/GEJ).

The randomised controlled trial will evaluate the anti-Dickkopf-1 (DKK1) antibody in combination with BeiGene’s anti-PD-1 antibody tislelizumab, and chemotherapy, versus a tislelizumab and chemotherapy control arm in these patients.

It will assess DKN-01, along with tislelizumab and standard of care (SOC) chemotherapy, in patients with inoperable, locally advanced, G/GEJ adenocarcinoma.

Part C of this trial will enrol nearly 160 first-line, HER2-negative patients, who will be randomised into a 1:1 ratio for evaluating DKN-01 in combination with tislelizumab and SOC chemotherapy, against tislelizumab and SOC chemotherapy.

Progression-free survival (PFS) in DKK1-high patients is the primary objective of the trial.

Part C’s secondary objectives include PFS in all subjects, irrespective of DKK1 expression, in addition to objective response rate and overall survival as measured by RECIST v1.1 in DKK1-high and all patients.

Leap Therapeutics chief medical officer Cynthia Sirard said: “The data to date from the DisTinGuish study show the DKN-01 plus tislelizumab combination therapy to be a compelling potential treatment for patients with G/GEJ cancer, with response rates and survival outcomes that exceeded the benchmarks.

“This first randomised controlled study for DKN-01 will characterise the treatment effect in first-line patients, with a particular emphasis on those in the aggressive DKK1-high population.”

The humanised monoclonal antibody DKN-01 attaches to and blocks the Dickkopf-1 (DKK1) protein activity.

The antibody secured Orphan Drug Designation from the US Food and Drug Administration for the treatment of gastric and gastroesophageal junction cancer.