On May 25, 2023 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that the Company will be presenting new long-term follow-up data in first-line patients with advanced gastric or gastroesophageal junction adenocarcinoma (GEA) from Part A of the DisTinGuish study, a Phase 2 clinical trial evaluating Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with BeiGene’s tislelizumab and chemotherapy, at the upcoming 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL on June 2-6, 2023 (Press release, Leap Therapeutics, MAY 25, 2023, View Source [SID1234632063]).

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"The long-term follow-up data for DKN-01 in combination with tislelizumab and chemotherapy indicates a novel and well-tolerated treatment with the potential for enhanced response rate, survival, and quality of life for advanced GEA patients," said Samuel Klempner, MD, Associate Professor at Harvard Medical School and principal investigator on the DisTinGuish study. "Median overall survival and progression-free survival for patients treated with DKN-01 plus tislelizumab and chemotherapy exceeded current PD-1 combination benchmarks, especially for those patients with low expression of PD-L1. Together with the previously reported data on the encouraging outcomes with DKN-01 for patients with high DKK1 expression, these results provide strong support for the ongoing randomized controlled clinical trial in first-line GEA patients."

"We are excited about the latest data from Part A of the DisTinGuish study which continues to show DKN-01 plus tislelizumab and chemotherapy as a safe and active treatment where tumor reductions can continue to deepen over time. It is extremely encouraging to see an additional patient achieve a partial response, which is ongoing, after 22 months on therapy," said Cynthia Sirard, MD, Chief Medical Officer of Leap Therapeutics. "A 90% overall response rate in DKK1-high patients and 86% overall response rate in PD-L1 low patients, both of which are associated with poor outcomes, along with 11.3 months median progression-free survival and 19.5 months median overall survival in the full population, demonstrates the important potential of DKN-01. We look forward to completing enrollment in the randomized controlled clinical trial late this year and seeing data from our ongoing colorectal cancer trial in the coming months."

Key Findings Part A DisTinGuish

· Median overall survival (OS) of 19.5 months and median progression-free survival (PFS) of 11.3 months exceeds benchmark results in the overall first-line patient population (n=25)

· Compelling OS and PFS results in all four important biomarker subgroups

○ 18.7 months OS and 10.7 months PFS in PD-L1-low (vCPS < 5) patients (n=16)
○ 22.0 months OS and 11.6 months PFS in PD-L1-high (vCPS > 5) patients (n=6)
○ 16.9 months OS and 11.3 months PFS in DKK1-high patients (n=12)
○ 24.4 months OS and 12.0 months PFS in DKK1-low patients (n=9)

· Additional patient with a partial response after 22 months on therapy improves objective response rate (ORR) to 73% in the overall modified intent-to-treat population (n=22), with one (5%) complete response (CR), 15 (68%) partial responses (PR), 5 (23%) best responses of stable disease (SD), and 1 (5%) non-evaluable (NE)

○ 86% ORR in PD-L1-low patients (n=14: 12 PR, 2 SD)
○ 67% ORR in PD-L1-high patients (n-6: 1 CR, 3 PR, 1 SD, 1 NE)
○ 90% ORR in DKK1-high patients (n=10: 9 PR, 1 NE)
○ 67% ORR in DKK1-low patients (n=9: 1 CR, 5 PR, 3 SD)
· Consistent with previous results, combination was well tolerated with manageable toxicity, with most adverse events related to DKN-01 being low-grade (76%)

Leap Poster Details:

Title: A phase 2 study (DisTinGuish) of DKN-01 in combination with tislelizumab + chemotherapy as first-line (1L) therapy in patients with advanced gastric or GEJ adenocarcinoma (GEA).

Presenter: Samuel J. Klempner, Harvard Medical School

Session Type: Poster Discussion Session

Session Title: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary

Date and Time: Monday, June 5, 2023, at 11:30 a.m. CT

Abstract Number: 4027

Poster Number: 335

About the DisTinGuish Study

The DisTinGuish study (NCT04363801) is a Phase 2 study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in three parts in the United States, the Republic of Korea, the United Kingdom, and Germany. Part A enrolled 25 first-line HER2- GEA cancer patients to receive DKN-01 in combination with tislelizumab and capecitabine and oxaliplatin. Part B enrolled 52 second-line GEA cancer patients whose tumors expressed high levels of DKK1 to receive DKN-01 in combination with tislelizumab. Part C is enrolling approximately 160 first-line HER2- GEA cancer patients in a randomized controlled trial of DKN-01 in combination with tislelizumab and chemotherapy compared to tislelizumab and chemotherapy. Tislelizumab is provided for the study through a clinical collaboration with BeiGene, Ltd.