The phase 2 DeFianCe study will evaluate the safety and efficacy of DKN-01 combined with bevacizumab and chemotherapy in patients with colorectal cancer vs becazixumab and chemotherapy alone.
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 CSirard@leaptx.com and Elizabeth Parker, eparker@leaptx.com
Completion Date: August 2024
The first patient has been enrolled in the phase 2 DeFianCe study (NCT05480306) of DKN-01 in combination with standard of care bevacizumab (Avastin) and chemotherapy as a second-line treatment for patients with advanced colorectal cancer (CRC).1
DKN-01 is a humanized monoclonal antibody created by Leap Therapeutics, Inc. The agent works to bind to and block the activity of the Dickkopf-1 (DKK1) protein, which plays an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immunosuppressive tumor microenvironment.
"We believe that DKN-01 has broad clinical potential. Based on the role of DKK1 in suppressing the immune system in the tumor microenvironment and enabling resistance to chemotherapy in CRC, we are excited to explore this new indication, one of the most frequent and dangerous types of GI cancers where patients continue to look for new treatment options," said Cynthia Sirard, MD, chief medical officer of Leap Therapeutics, in the press release. "Enrolling the first CRC patient is an important milestone for the DKN-01 clinical program, and we look forward to reporting initial data from this study in mid-2023."
The DeFianCe study is a randomized, open-label, multicenter, 2-part study of DKN-01 combined with bevacizumab and chemotherapy in patients with advanced CRC who have received one prior systemic therapy.2
Parts A and B of the trial will enroll approximately 150 evaluable patients with CRC, including an initial 20 patient cohort which will then expand to include 130 patients to examine the efficacy and safety of DKN0-01 with or without bevacizumab and standard of care chemotherapy.
Enrollment is open to patients aged 18 years and older with CRC who have disease progression following first-line systemic therapy with any fluoropyrimidine-based regimen, except FOLFOXIRI. Patients must have 1 or more tumors measurable on radiographic imaging, sufficient tumor tissue for mandatory pre-treatment evaluation, an ECOG performance status of 0-1 within 7 days of treatment with the first dose of DKN-01, and agree to use adequate contraception during the time of the study until 6 months after the last dose of the study drug
Patients in the experimental arm will be administered DKN-01 by a 30 minute intravenous (IV) infusion of 400mg 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) followed by a continuous 46 hour infusion of fluorouracil every 2 weeks. Those in the control arm will be given a matching treatment excluding DKN-01.
The primary end point of the trial is progression-free survival with 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.
The trial is actively recruiting in Maryland and has a planned study completion date of August 2024. Initial data from the trial is expected to be reported in the middle of 2023.
