Leap Therapeutics has enrolled the first subject in the Phase II DeFianCe clinical trial of its anti-Dickkopf-1 antibody (DKK1) DKN-01 plus standard-of-care bevacizumab and chemotherapy as a second-line treatment for advanced colorectal cancer (CRC) patients.

The open-label, randomised, multicentre trial will assess the combination treatment in advanced CRC patients who have previously received a systemic therapy.

In the initial stage, the trial will have a 20-subject cohort and will subsequently be expanded into a 130-subject controlled, randomised trial against bevacizumab and standard-of-care chemotherapy.

Progression-free survival is the primary objective of the trial.

Overall response rate, duration of response and overall survival comprise the trial’s secondary objectives.

The company anticipates reporting the preliminary findings from the trial mid-next year.

A humanised monoclonal antibody, DKN-01 attaches to and hinders the DKK1 protein’s activity.

It is under development for esophagogastric, gynaecologic and colorectal cancers.

The company has signed a strategic partnership with BeiGene for the rights for developing DKN-01 in Australia, New Zealand and Asia excluding Japan.

Leap Therapeutics chief medical officer Cynthia Sirard said: “We believe that DKN-01 has broad clinical potential.

“Based on the role of DKK1 in suppressing the immune system in the tumour microenvironment and enabling resistance to chemotherapy in CRC, we are excited to explore this new indication, one of the most frequent and dangerous types of GI cancers where patients continue to look for new treatment options.”

Colorectal cancer is the third most prevalent cancer worldwide and comprises colon, rectal and anal cancers.

Most patients are at an advanced stage when the CRC symptoms such as rectal bleeding, anaemia, or abdominal pain occur.

The latest development comes after the company enrolled the first patient in Part C of the DisTinGuish Phase II trial of DKN-01 along with tislelizumab for gastric or gastroesophageal junction cancer.