Benzinga | Nov 9, 2020 08:45AM EST

Leap Therapeutics Highlights Presentation Of Updated Data For DKN-01 In Esophagogastric Cancer Patients At Society for Immunotherapy Of Cancer Meeting

Leap Therapeutics, Inc. (NASDAQ:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced the presentation of clinical data from its Phase 1b/2a clinical trial of DKN-01 in patients with advanced esophagogastric cancer (EGC) at the Society for Immunotherapy of Cancer's 35th Anniversary Annual Meeting. DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein.



In the study, high levels of tumoral DKK1 expression correlated with improved clinical outcomes in heterogeneous EGC patients treated with DKN-01 as monotherapy or in combination with pembrolizumab or paclitaxel. Pooled data for the 69 patients in the study for whom tumoral DKK1 expression data is available demonstrated that DKK1-high patients experienced higher overall response rates (ORR), a doubling of median progression-free survival (PFS), and longer median overall survival (OS) as compared to DKK1-low patients. Additionally, DKK1-high anti-PD-1/PD-L1 refractory patients treated with DKN-01 plus pembrolizumab experienced longer PFS and OS compared to DKK1-low patients, suggesting that DKK1 tumoral expression may serve as a predictive biomarker to identify patients for treatment with DKN-01 in combination with anti-PD-1 antibodies. No notable differences were found in baseline MSS, TMB, or PD-L1 expression between DKK1-high versus DKK1-low groups.

"We continue to observe clinically meaningful activity of DKN-01 in patients with advanced previously treated esophagogastric cancer that reinforces our belief that elevated tumoral DKK1 expression is a predictive biomarker for improved outcomes, particularly for those patients treated with DKN-01 in combination with an anti-PD-1 antibody," said Samuel J. Klempner, MD, Assistant Professor, Massachusetts General Hospital Cancer Center and Harvard Medical School.

"We believe that the totality of the results from this study provides strong support for the ongoing study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, in DKK1-high second line gastroesophageal junction and gastric cancer (GEJ/GC) patients and in combination with tislelizumab, capecitabine, and oxaliplatin in first-line GEJ/GC patients," continued Dr. Klempner.

The P102 Study in Relapsed or Refractory Esophagogastric Cancer

The P102 study (KEYNOTE-731) is a multi-part Phase 1/2 study of DKN-01 as a monotherapy and in combination with paclitaxel or KEYTRUDA(r) (pembrolizumab) in advanced EGC patients, with a median of two previous treatments with standard therapies, representing a difficult to treat population. The study is intended to establish the safety and activity of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab, with efficacy endpoints of ORR, PFS, and OS. Tumoral DKK1 expression was determined retrospectively by RNAscope(r) chromogenic in situ hybridization and correlated with clinical outcomes. Pembrolizumab was provided for the study through a clinical trial collaboration agreement with Merck (known as MSD outside the United States and Canada).

Key DKN-01/Pembrolizumab Findings from the P102 Study

* Anti-PD-1/PD-L1 refractory patients (all): The four DKK1-high patients had a significantly longer PFS of 12.8 weeks and OS of 46 weeks as compared to the five DKK1-low patients who experienced PFS of 6 weeks and OS of 16 weeks.

* Anti-PD1/PD-L1 refractory GEJ/GC patients: The three DKK1-high patients had a best response of stable disease (SD) and a longer PFS of 13.4 weeks and OS of 37.4 weeks, as compared to the two DKK1-low patients who both had progressive disease (PD) with a PFS of 3.6 weeks and OS of 11.7 weeks.

* Anti-PD-1/PD-L1 na?ve GEJ/GC patients: As previously reported, DKK1-high patients experienced over 22 weeks PFS and nearly 32 weeks OS, with a 50% overall response rate and 80% disease control rate (DCR) in ten evaluable patients. DKK1-low patients experienced nearly 6 weeks PFS and over 17 weeks OS, with a 20% DCR in fifteen evaluable patients. PD-L1 Combined Positive Scores (CPS) did not predict efficacy on the combination of DKN-01 plus pembrolizumab. In multi-variate analysis, DKK1-high status correlated with longer PFS independent of PD-L1 CPS scores.