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About the DeFianCe Trial
Trial Name: Randomized Phase 2 Study of DKN-01 Plus FOLFIRI/FOLFOX and Bevacizumab Versus FOLFIRI/FOLFOX and Bevacizumab as Second-line Treatment of Advanced Colorectal Cancer (DeFianCe)
ClinicalTrials.gov Identifier: NCT05480306
Sponsor: Leap Therapeutics, Inc.
Recruitment Contact: Cynthia Sirard, MD, (617) 714-0357, email@example.com, and Elizabeth Parker, firstname.lastname@example.org
Completion Date: August 2024
The first part of the phase 2 DeFianCe trial (NCT05480306) evaluating DKN-01 in combination with standard of care bevacizumab (Avastin) and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC) has completed enrollment, according to Leap Therapeutics, Inc.1
“DKN-01 is a drug that is able to bind to and reverse the pro-tumorigenic effects of DKK1. DKN-01 slows tumor growth, blocks immunosuppressive cells in the tumor microenvironment, reduces blood vessel growth near the tumor, and activates certain types of anti-tumor immune cells,” John Strickler, MD, associate professor of medicine at Duke University Medical Center, told Targeted OncologyTM, in an interview.
The anti-DKK1, humanized monoclonal antibody, DKN-01 attaches to and blocks the activity of the DKK1 protein. DKN-01 is able to activate NK cells, reduce immune suppressor cells, and stimulate an immune-mediated anti-tumor response by removing free DKK1 from the tumor microenvironment.
DKN-01 is being assessing in the randomized, open-label, multicenter, phase 2 DeFianCe study (NCT05480306) in combination with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received 1 prior systemic therapy for advanced disease.
The initial part A cohort of the trial enrolled 33 patients and is designed to expand into a 130-patient Part B randomized controlled trial to examine the efficacy and safety of DKN0-01 with or without bevacizumab and standard of care chemotherapy.2
In the experimental arm of the trial, DKN-01 will be given to patients via a 30 minute intravenous (IV) infusion of 400 mg every 2 weeks with an additional loading dose in the first cycle of treatment, 90 minute IV infusion of irinotecan, leucovorin, and fluorouracil (FOLFIRI) followed by a continuous 46 hour infusion of fluorouracil every 2 weeks, bevacizumab at 5 mg by a 90 minute IV infusion, and a 2 hour IV infusion of oxaliplatin, folinic acid, and fluorouracil (FOLFOX), as well as a continuous 46 hour infusion of fluorouracil every 2 weeks. The control arm will administer patients a matching treatment excluding DKN-01.
Investigators are assessing the primary end point of progression-free survival and secondary end points of overall response rate, duration of response, overall survival, and safety. Additional end points include duration of complete response, duration of clinical benefit, disease control rate, time to response, and exposure-response relationships for DKN-01.
In addition to the DeFianCe study, DKN-01 is being evaluated in the randomized controlled DisTinGuish study (NCT04363801). This trial is assessing the agent in combination with tislelizumab (BGB-A317) and chemotherapy in patients with first-line gastric cancer. Additionally, DKN-01 is being evaluated in an investigator-sponsored trial in combination with pembrolizumab (Keytruda) for patients with advanced endometrial cancer (NCT03395080).1
"The completion of enrollment of part A of the DeFianCe study is an important milestone for the DKN-01 colorectal cancer development program," said Cynthia Sirard, MD, chief medical officer of Leap, in the press release. "We were very pleased with the enthusiasm of our investigators and patients for participating in part A, which reflects the unmet medical need of second-line CRC patients and their conviction in the DKN-01 preclinical data and mechanism of action. We look forward to initial data from the study in mid-2023."
1. Leap Therapeutics announces completion of enrollment in part A of the DeFianCe study of DKN-01 for the treatment of colorectal cancer patients. News release. Leap Therapeutics, Inc. April 12, 2023. Accessed April 18, 2023. https://prn.to/3mNCmLtPhase 2 study of DKN-01 in colorectal cancer (DeFianCe). ClinicalTrials.gov. Updated April 7, 2023. Accessed April 18, 2023. https://clinicaltrials.gov/ct2/show/NCT05480306