On January 18, 2022 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported that 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) (Free ASCO Whitepaper) Gastrointestinal (GI) Cancers Symposium being held on January 20-22, 2022 (Press release, Leap Therapeutics, JAN 18, 2022, View Source [SID1234605541]).

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The Company will host a conference call with Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital on Friday, January 21, 2022 to discuss results from the study.

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.

"The combination of DKN-01 with tislelizumab continues to demonstrate encouraging results in patients with gastric and gastroesophageal junction cancer, especially those in the DKK1-high subpopulation," said Samuel Klempner, MD, Associate Professor at Harvard Medical School who leads the gastric and esophageal cancer program at Massachusetts General Hospital Cancer Center and is a principal investigator on the DisTinGuish study. "The updated front-line results are encouraging in a difficult to treat cohort of primarily PD-L1 low patients, who are less likely to benefit from anti-PD-1 therapy. Together with encouraging initial findings from Part B, where DKN-01 and tislelizumab are used as a chemo-free second-line treatment of DKK1 high-expressing tumors, these results continue to support the therapeutic potential of DKN-01 and warrant exploration in a randomized clinical trial in first-line gastric and gastroesophageal junction patients."

About the DisTinGuish Study

The DisTinGuish study (NCT04363801) is a Phase 2a 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 two parts in the United States and the Republic of Korea. Enrollment of Part A has been completed with 25 first-line HER2- G/GEJ cancer patients whose tumors express either high levels of DKK1 (DKK1-high) or low levels of DKK1 (DKK1-low). Part B of the study has enrolled 30 patients with second-line DKK1-high G/GEJ cancer and will continue to enroll up to 48 patients. Leap is conducting this combination study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.

First-Line Part A Key Findings

· Overall preliminary median progression-free survival (PFS) was 10.7 months
o 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)
o 90% ORR in DKK1-high patients (n=10)
o 56% ORR in DKK1-low patients (n=9)
· Activity was independent of PD-L1 expression
o 79% ORR in PD-L1-low (vCPS < 5) and 67% ORR in PD-L1-high (vCPS > 5) patients
o 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.

Leap Presentation Details:

Title: DKN-01 and Tislelizumab ± Chemotherapy as a First-Line (1L) and Second-Line (2L) Investigational Therapy in Advanced Gastroesophageal Adenocarcinoma (GEA): DisTinGuish Trial

Session Type: Poster Session

Presenter: Samuel J. Klempner, Harvard Medical School

Date and Time: Thursday, January 20, 2022 at 3:00 p.m. Eastern Time

Conference Call

Leap will host a conference call on Friday, January 21, 2022 at 1:00 p.m. Eastern Time to further discuss the data. In addition to Leap’s executive management team, Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital will be on the call. The call can be accessed by dialing (866) 589-0108 (U.S. and Canada) or (409) 231-2048 (international). The passcode for the conference call is 3323348. The presentation will be webcast live and may be accessed on the Investors page of the Company’s website at View Source, where a replay of the event will also be available for a limited time.

About DKN-01

DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.