Leap Therapeutics has reported positive results from the KEYNOTE-731 clinical trial of its anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with Merck‘s anti-PD-1 antibody, Keytruda (pembrolizumab).

The trial demonstrated higher survival and objective response outcomes in patients with advanced gastroesophageal junction and gastric cancer (GEJ/GC).

The DKN-01 and Keytruda combination treatment achieved more than 22 weeks median progression-free survival (PFS) and 32 weeks median overall survival (OS) with a 50% overall response rate (ORR) and 80% disease control rate (DCR).

DKK1-low patients experienced roughly six weeks median PFS and over 17 weeks OS, with a 20% DCR in 15 evaluable patients.

Massachusetts General Hospital Cancer Center and Harvard Medical School assistant professor Samuel Klempner said: “The responses and early survival data seen in DKK1-high patients treated with DKN-01 plus pembrolizumab are highly encouraging.

“This study builds on previously reported positive monotherapy and paclitaxel combination data and importantly suggests that elevated DKK-1 expression is a potential predictive biomarker.”

The esophagogastric cancer clinical trial, KEYNOTE-731, is a multipart study of DKN-01 as a monotherapy and in combination with paclitaxel or pembrolizumab.

A total of 63 GEJ/GC patients received DKN-01 and Keytruda combination therapy across all arms and dose groups of the study.

The combination demonstrated improved outcomes in patients whose tumors are DKK1-high and who were PD-1/PD-L1 naïve.

PD-L1 Combined Positive Scores (CPS) did not predict efficacy on the combination.

Among the six GEJ/GC patients who were refractory to PD-1/PD-L1 therapy, three DKK1-high patients had the best response of stable disease.

The three patients with DKK1-low tumours had progressive disease.

In June 2017, Leap Therapeutics signed a clinical trial collaboration agreement with Merck to investigate DKN-01 in combination with Keytruda.