Following early efficacy demonstrated with DKN-01, bevacizumab, and chemotherapy in part A of the DeFianCe study, part B has begun enrolling patients with advanced colorectal cancer.
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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
Enrollment of patients in part B of the phase 2 DeFianCe study (NCT05480306) evaluating the anti-Dickkopf-1 (DKK1) antibody 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 begun.1
The enrollment of patients in part B follows early efficacy and momentum seen among 33 patients in the first part of the study.
Part B of the open-label, phase 2 study is expected to be completely enrolled in approximately 12 months. Initial data are anticipated to be announced in late 2024.
"Part A of the DeFianCe study enrolled an aggressive heterogeneous population of [patients with] second-line CRC representative of the second-line population that we see in the clinic who have poor outcomes on standard of care drugs and are in need of new therapies," said Zev Wainberg, MD, professor medicine at UCLA and co-director of the UCLA GI Oncology Program, in a press release. "Exceeding a 20% overall response rate with a high disease control rate in [patients with] second-line CRC is a clinically meaningful efficacy signal and worthy of further exploration."
The DeFianCe study is investigating the combination of DKN-01 with standard of care bevacizumab and chemotherapy in patients with advanced CRC who have received previously received 1 systemic therapy for advanced disease.2
In part A cohort, 33 patients were enrolled, including those who had early progression on first-line therapy, previous exposure to bevacizumab, tumors harboring RAS mutations, or liver metastases. Now, the study has expanded and is enrolling 130 patients in part B.
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 for advanced disease, excluding folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI). Patients are required to have received prior neoadjuvant or adjuvant therapy, have 1 or more tumors measurable on radiographic imaging as defined by RECIST 1.1, sufficient tumor tissue for mandatory pre-treatment evaluation, an ECOG performance status ≤1 within 7 days of receiving the first dose treatment, and acceptable liver, renal, hematologic, and coagulation function.
Additionally, female patients of childbearing potential as well as male partners of female patients must use adequate contraception during the duration of the trial and for 6 months after they have received their last dose.
The primary end point being evaluated in the study is progression-free survival. Secondary end points include overall response rate, duration of response, overall survival, and incidence of ≥ grade 3 related treatment-related adverse events. Other objectives being assessed are duration of complete response, clinical benefit, disease control rate, time to response, and exposure-response relationships for DKN-01 as data permit.
"The study enrolled quickly and has already exceeded the 20% overall response rate threshold. After the planned safety review meeting with our investigators, we decided to initiate the randomized controlled study," said Cynthia Sirard, MD, chief medical officer of Leap Therapeutics, in the press release.1 "We continue to follow these part A patients to assess durability of response, progression-free survival, and to determine whether additional patients with stable disease may become responders over time. We very much look forward to presenting this maturing data set at an upcoming meeting."
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