Leap Therapeutics, Inc. announced the Company will be presenting updated data from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap's anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene's anti-PD-1 antibody, in patients with gastric or gastroesophageal junction cancer (G/GEJ), at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium being held on January 20-22, 2022. The latest results from Part A of the DisTinGuish study will be presented, representing first-line advanced G/GEJ patients treated with DKN-01 in combination with tislelizumab and chemotherapy. New data demonstrate compelling efficacy from this combination regimen, driven by enhanced clinical responses and survival benefit associated with high tumoral DKK1 expression that is independent of PD-L1 expression.

Also to be presented are initial findings from the still-enrolling Part B of the clinical trial, studying DKN-01 and tislelizumab in second-line advanced G/GEJ patients with high tumoral DKK1 expression, showing the treatment is well tolerated with encouraging objective responses observed. First-Line Part A Key Findings: Overall preliminary median progression-free survival (PFS) was 10.7 months; PFS was longer in DKK1-high patients at 11.9 months, compared to 10.7 months in DKK1-low patients. Preliminary median duration of response (DoR) was 10.7 months in DKK1-high patients, compared to 7.9 months in DKK1-low patients.

Median overall survival has not been reached. Among patients who received a full first cycle of DKN-01 (modified intent to treat, n=22), the objective response rate (ORR) was 68%, including one complete response (CR) and 14 partial responses (PR). 90% ORR in DKK1-high patients (n=10).

56% ORR in DKK1-low patients (n=9). Activity was independent of PD-L1 expression. 79% ORR in PD-L1-low (vCPS < 5) and 67% ORR in PD-L1-high (vCPS > 5) patients.

100% ORR in DKK1-high, PD-L1-low patients (n=6). Combination was well tolerated, safety profile consistent with previous update and reflecting the underlying patient population. Second-Line Part B Key Findings: DKN-01 and tislelizumab administered in DKK1-high, PD-1 naïve patients was well tolerated at both 300mg and 600mg DKN-01 doses.

Among evaluable patients who received a full first cycle of DKN-01 (response evaluable modified intent to treat, n=20), the objective response rate (ORR) was 25%, including 5 PRs and 4 stable disease (SD). One additional patient has had an irPR by iRECIST criteria. PD-L1 expression is low overall in the study population and not correlated with DKK1 expression.

The study is ongoing and enrolling in the 600mg DKN-01 cohort. Twelve patients were on study at the time of the data cut, four of whom had not yet had their first imaging assessment.