Leap’s DKN-01 Enters Testing in Metastatic Castration-resistant Prostate Cancers

Leap Therapeutics is launching a Phase 1/2 trial to study its lead candidate DKN-01, alone or in combination with chemotherapy, for the treatment of metastatic castration-resistant prostate cancer (CRPC) patients whose tumors have elevated Dickkopf-1 (DKK1) levels.

The trial (NCT03837353), led by David Wise, MD, PhD, will be conducted at the Perlmutter Cancer Center at NYU Langone Health and is expected to begin around the end of March.

“Patients with this type of prostate cancer have a very poor prognosis and may benefit from this new immunotherapy strategy targeting DKK1 therapy with DKN-01,” Wise said in a press release.

The DKK1 protein is often elevated in cancers, leading to more aggressive tumors, poor immune responses, and worse outcomes.

The protein plays an important role in controlling the Wnt signaling pathway, a key player during embryonic development that regulates crucial aspects of cell fate and proliferation. Aberrant Wnt activity enables cancer cells to grow uncontrolled and creates an immunosuppressive environment surrounding tumors.

Thus, DKK1 inhibition might have a dual anti-cancer mechanism, causing cancer cell death directly and boosting the immune system to fight cancers. Consistently, Leap’s DKN-01, an anti-DKK1 antibody, has been found to have potent anti-cancer activity, working well in combination with chemotherapies and immune checkpoint inhibitors.

“DKK1 can promote prostate cancer growth through suppressing the anti-tumor immune response. We have discovered that DKK1 is upregulated in the substantial portion of advanced prostate cancers that lack expression of androgen receptor,” Wise said.

The upcoming clinical trial will include 97 metastatic CRPC patients whose tumors continued to progress despite treatment with one or more androgen receptor therapies — Zytiga (abiraterone acetate) and Xtandi (enzalutamide). Eligible participants must have elevated DKK1 levels,  measured in blood or tumor samples.

“An important part of our DKN-01 development strategy is to target biomarker-selected patient populations,” said Cynthia Sirard, MD, Leap’s vice president of clinical development.

“In our esophagogastric cancer study, we have identified DKK1 levels measured by RNAScope as a potential predictor of response to DKN-01-based therapy. We are looking forward to treating mCRPC patients with elevated DKK1 levels in this study, building on our and Dr. Wise’s work,” Sirard said.

In the trial, patients who have not received a prior taxane-based chemotherapy will be given a combination of DKN-01 and Taxotere (docetaxel); those who progressed or refused Taxotere treatment will receive DKN-01 alone.

The main goals are to study DKN-01’s safety, tolerability, and preliminary signs of efficacy in this patient population.