On September 15, 2021 Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the presentation of updated positive data from the first-line cohort of the DisTinGuish study, a Phase 2a clinical trial evaluating Leap’s anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene Ltd.’s anti-PD-1 antibody, and chemotherapy, in patients with gastric or gastroesophageal junction cancer (G/GEJ), at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (Press release, Leap Therapeutics, SEP 15, 2021, View Source [SID1234587771]). The Company will host a conference call on Friday, September 17, 2021 to discuss preliminary results from the study.
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The Company announced positive initial data from the DisTinGuish study on Monday, September 13, 2021 based on 25 G/GEJ patients enrolled in the trial that showed DKN-01 in combination with tislelizumab and chemotherapy as first-line therapy was well tolerated with compelling activity. The results presented at the ESMO (Free ESMO Whitepaper) Congress today included additional patient data stratified by tumoral PD-L1 expression levels based on visually-estimated combined positive score (vCPS), showing that robust objective clinical responses can be achieved from this combination regimen independently of PD-L1 expression.
"Initial data from this trial have shown that patients with high levels of DKK1 expression, a group with a poor prognosis, had encouraging responses to treatment. The additional data presented today show evidence that not only is DKK1 a critical biomarker in predicting response to DKN-01 and tislelizumab therapy, but also that the combination can induce deep responses regardless of the patient’s PD-L1 status, including particularly poor prognosis patients with both low PD-L1 and high DKK1," said Samuel Klempner, MD, Member of the Faculty at Massachusetts General Hospital Cancer Center and Harvard Medical School. "Taken together, these are promising results for the combination therapy of DKN-01 with tislelizumab and chemotherapy in first line patients with gastric or gastroesophageal junction cancers."
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 will enroll up to 48 patients with second-line, DKK1-high G/GEJ cancer. 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.
Key Findings
Among patients who received a full cycle of DKN-01 therapy, the ORR was 68.2%, with 90% ORR in DKK1-high patients and 56% in DKK1-low patients
Response was independent of PD-L1 expression, and particularly strong in the less favorable to checkpoint inhibitor therapy, PD-L1 low (vCPS < 5), population
Among those patients with PD-L1-low expression (vCPS < 5), the ORR was 79%, with 100% in DKK1-high patients and 57% in DKK1-low patients
Among those patients with PD-L1-high expression (vCPS ≥ 5), the ORR was 67%, with 75% ORR in DKK1-high patients and 50% in DKK1-low patients
DKK1 levels could not be determined in one patient who had PD-L1 expression data; however, the patient’s PD-L1 expression level was determined to be low (vCPS score 0) and the patient achieved a partial response
DKK1 expression and PD-L1 expression are not correlated
Median duration of response and progression-free survival data are not yet mature, and patient follow-up continues
Twenty-five first-line patients were enrolled, and as of the cut-off date of the presentation, 15 patients had experienced a partial response (PR), six patients had a best response of stable disease (SD), one patient was non-evaluable for response (NE), and three patients were unable to complete a full cycle of DKN-01 therapy (non-modified ITT (mITT)).
Among the 21 patients that had RNAscope DKK1 expression available, 12 were DKK1-high [9 PR, 1 NE, 2 non-mITT] and 9 were DKK1-low [5 PR, 4 SD].
Among the 20 patients that had PD-L1 expression available, 14 were PD-L1 low vCPS < 5 [11 PR, 3 SD] and 6 were PD-L1 high vCPS > 5 [4 PR, 1 SD, 1 NE].
A copy of the poster presentation is available on the Company’s website at View Source
Conference Call
Leap will host a conference call on Friday, September 17, 2021 at 8:00 a.m. Eastern Time to further discuss the data. In addition to Leap’s executive management team, Dr. Jaffer Ajani of M.D. Anderson Cancer Center and Dr. Samuel Klempner of 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 1729397. 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.