DisTinGuish Trial Starts Enrollment of Patients with Gastric/GEJ Cancers

The first patient with gastric or gastroesophageal junction (GEJ) cancer has been enrolled to the phase 2 DisTinGuish study (NCT04363801) of DKN-01 in combination with tislelizumab and standard of care (SOC) chemotherapy, Leap Therapeutics announced, in a press release.¹

DisTinGuish aims to enroll 160 patients with HER2-negative disease who require frontline treatment. Patients enrolled will be randomized 1:1 to receive either DKN-01 with tislelizumab and SOC chemotherapy or tislelizumab plus SOC chemotherapy. The primary end point of the study is progression-free survival (PFS) in patients with DKK1-high tumors. The secondary end points of the study include PFS in all patients regardless of DKK1 expression, overall survival (OS), and objective response rate (ORR) by RECIST v1.1 in the DKK1-high population and in all patients.^1,2

Intravenous DKN-01 is administered at 300 mg on days 1 and 15 in combination with tislelizumab 200 mg on day 1. SOC chemotherapy in the study consists of intravenous (IV) oxaliplatin 130 mg/m² administered on day 1, and oral capecitabine 1000 mg/m2 twice daily administered on days 1-15 of each 21-day cycle.²

"We are excited to announce another important milestone for our DKN-01 clinical program in combination with our partner BeiGene's tislelizumab, advancing this unique combination therapy into part C of the DisTinGuish study," said Cynthia Sirard, MD, chief medical officer of Leap Therapeutics,” in the press release.¹

The study will be conducted in 2 parts to investigate the combination in patients who are treatment-naïve and patients who are previously treated but developed progressive disease in the first-line setting. To be eligible for enrollment, patients in part A must have not received prior treatment for cancer but have received prior neoadjuvant or adjuvant therapy without disease recurrence for at least 6 months. To be eligible for part B, patients must have progressed on frontline therapy or within 4 months after the last dose of first-line therapy.²

Patients enrolling into either part A or part B of the study must have a confirmed diagnosis of gastric adenocarcinoma or GEJ adenocarcinoma, measurable disease per RECIST v1.1, an ECOG performance status of ≤ 1 within 7 days of first dose of the study drugs, as well as acceptable liver, renal, hematologic, and coagulation function.

Criteria for DisTinGuish excludes patients with HER2-positive disease and who are unable to swallow medication from part A. Patients are also ineligible to enroll in part B is the have undergone major surgery or chemotherapy within 21 days of the first dose of treatment in the study. Patients are excluded from any part of the study if they were previously treated with radiation therapy within 14 day of study entry, an anti-DKK1 therapy, PD-1/PD-L1/PD-L2 therapy, live vaccine within 28 days of the first treatment in the study or have infections or comorbidities that may interfere with the safety and effectiveness of study treatment.

Currently, 32 study sites around the world are recruiting patients for the DisTinGuish study.

"The data to date from the DisTinGuish study show the DKN-01 plus tislelizumab combination therapy to be a compelling potential treatment for patients with G/GEJ cancer with response rates and survival outcomes that exceeded the benchmarks. This first randomized controlled study for DKN-01 will characterize the treatment effect in first-line patients, with a particular emphasis on those in the aggressive DKK1-high population,” said Sirard.¹

_REFERENCES:

_{1. Leap Therapeutics announces first patient enrolled in part c of phase 2 DisTinGuish Study of DKN-01 in combination with tislelizumab for the treatment of gastric or gastroesophageal junction cancer. News release. October 12, 2022. https://bit.ly/3yzZe3I}

_{2. A study of DKN-01 in combination with tislelizumab ± chemotherapy in patients with gastric or gastroesophageal cancer (DisTinGuish). Clinicaltrials.gov. Updated April 25, 2022. Accessed October 12, 2022.}