About the Phase 2 DisTinGuish Study
Trial Name: A Phase 2a, Multicenter, Open-Label Study of DKN-01 in Combination With Tislelizumab ± Chemotherapy as First-Line or Second-Line Therapy in Adult Patients With Inoperable, Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (DisTinGuish))
ClinicalTrials.gov Identifier:NCT04363801
Sponsor: Leap Therapeutics, Inc. (Collaborator: BeiGene).
Recruitment Contact: Cynthia Sirard, MD 617-714-0357 CSirard@leaptx.com
Completion Date: December 2025
Part C of the DisTinGuish study (NCT0436380) evaluating DKN-01 combined with tislelizumab (Tevimbra) and chemotherapy in patients with advanced gastroesophageal junction (GEJ) and gastric cancer has completed enrollment.1
This part of the DisTinGuish study is a randomized, open-label, multicenter study evaluating this combination with DKN-01, tislelizumaband chemotherapy for the first-line treatment of patients with advanced gastroesophageal adenocarcinoma. A total of 170 patients with first-line, HER2-negative disease were enrolled in part C of the trial.
With the completion of enrollment in this part of the phase 2 study, investigators expect initial data to be presented throughout the year.
"The completion of enrollment in part C of the DisTinGuish study is an important milestone and continues to underscore the high level of interest from both patients and investigators in DKN-01," said Cynthia Sirard, MD, chief medical officer of Leap Therapeutics, in a press release. "Long-term follow-up data from part A of the study clearly demonstrated the potential to induce durable responses and clinically meaningful survival outcomes in first-line advanced gastroesophageal junction and gastric cancer patients. We expect part C to further validate the potential of DKN-01 and tislelizumab combination therapy and look forward to having initial data from part C over the course of this year.”
The phase 2 study randomly assigned patients in a 1:1 ratio with parts A and B designed to evaluate safety, tolerability, and efficacy of the combination of DKN-01 given via intravenous infusion plus tislelizumab with or without chemotherapy in patients with gastric/GEJ adenocarcinoma. For parts A and B, treatment will continue in repeating 21-day cycles until the patient meets criteria for discontinuation or is no longer deriving clinical benefit.2
Part C is designed to evaluate the efficacy and safety of tislelizumab with a chemotherapy regimen with or without DKN-01 in adult patients with inoperable, histologically confirmed locally advanced or metastatic gastric or GEJ adenocarcinoma with measurable disease requiring therapy.
Patients aged 18 years and older who have received no previous therapy for cancer were eligible for enrollment in the study. Patients were eligible if they had received prior neoadjuvant or adjuvant therapy as long it was completed without disease recurrence for at least 6 months since the last treatment. Across all parts of the study, patients must have had a confirmed diagnosis of gastric or GEJ adenocarcinoma, 1 or more tumors measurable on radiographic imaging as defined by RECIST 1.1., tumor tissue for pre-treatment evaluation, an ECOG performance status ≤ 1 within 7 days of the first dose of study drug, and acceptable liver, renal, hematologic, and coagulation function.
For part B of the study, patients must have had disease progression during first-line therapy or within 4 months after the last dose of first-line therapy and documented elevated DKK1 mRNA expression from a fresh tumor biopsy or a biopsy obtained within the 6 months of screening. Enrollment in part C was then only open to patients who had documentation of PD-L1 combined positive score by immunohistochemistry and DKK1 mRNA expression in tumor cells by in situ hybridization from a fresh tumor biopsy or archived tumor biopsy specimen conducted in a sponsor designated central laboratory.
The primary end point of the study is progression-free survival in DKK1-high and in all patients, and secondary end points of part C are overall survival and objective response rate.
REFERENCES
Leap Therapeutics announces completion of enrollment in randomized controlled part C of the DisTinGuish study of DKN-01 for the treatment of gastric cancer patients. News release. Leap Therapeutics, Inc. January 2, 2024. Accessed January 3, 2024. http://tinyurl.com/3bphysuw
A study of DKN-01 in combination with tislelizumab ± chemotherapy in patients with gastric or gastroesophageal cancer (DisTinGuish). ClinicalTrials.gov. Updated September 29, 2023. Accessed January 3, 2024. https://clinicaltrials.gov/study/NCT04363801
