공고 • Jun 03
Cardiff Oncology Announces Positive Results From Randomized Controlled Phase 2 Trial Of Onvansertib In First-Line RAS-Mutated mCRC
Cardiff Oncology, Inc. announced positive results from CRDF-004, a randomized, controlled, dose-finding Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care regimens (FOLFIRI/bevacizumab or FOLFOX/bevacizumab) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC). Results showed that the selected dose/regimen of the registrational program, onvansertib 30 mg + FOLFIRI/bevacizumab, demonstrated deep and durable tumor shrinkage, including clinically meaningful improvements in overall response rate (ORR) and progression-free survival (PFS) compared to standard-of-care alone, with no additive adverse events. The trial achieved its primary goal of selecting the efficacious and safe dose of onvansertib + standard-of-care regimen for the registrational program. The 30 mg onvansertib + FOLFIRI/bevacizumab arm showed a dose-dependent improvement in efficacy, including confirmed ORR of 72.2% compared to 42.1% for standard-of-care. Median PFS has not been reached in either 20 or 30 mg onvansertib + FOLFIRI/bevacizumab arm, with nine of the 14 patients remaining on treatment in these arms. Onvansertib continues to be safe and well-tolerated with no overlapping or new toxicities when added to standard-of-care. Registrational trial planned in first-line RAS-mutated mCRC following successful End-of-Phase 2 meeting with FDA. The randomized, controlled Phase 3 trial will evaluate the safety and efficacy of onvansertib 30 mg + FOLFIRI/bevacizumab as first-line therapy versus standard-of-care FOLFIRI/bevacizumab in patients with RAS-mutated mCRC. Data Highlights from the ongoing Phase 2 trial (Data cut: March 18, 2026): In the intent-to-treat (ITT) population, the dose selected for the registrational program, 30 mg onvansertib arm in combination with FOLFIRI/bevacizumab achieved: Primary endpoint of confirmed objective response rate of 72.2% (13/18), compared with 42.1% (8/19) for FOLFIRI/bevacizumab alone, a 30% improvement over standard-of-care. The responses were deeper and more durable in the onvansertib arm. Secondary endpoint of progression free survival (PFS) hazard ratio (HR) of 0.55 (95% CI: 0.15–2.09) and 0.57 (95% CI: 0.20–1.65) vs. FOLFIRI/bevacizumab by Blinded Independent Central Review (BICR) and investigator assessment (IA), respectively. Median PFS not reached in 30 mg onvansertib + FOLFIRI/bevacizumab arm, but has been reached in both standard-of-care arms. Four patients remain on onvansertib treatment beyond 15 months, including 2 beyond 20 months. Fourteen patients remain on trial, with nine patients in the onvansertib (20 or 30 mg) plus FOLFIRI/bevacizumab arms and one patient remaining on standard-of-care. No meaningful differences in efficacy were observed between the onvansertib + FOLFOX/bevacizumab arms and FOLFOX/bevacizumab alone. Onvansertib in combination with both chemotherapy (FOLFIRI or FOLFOX)/bevacizumab regimens was well-tolerated. There were no major or unexpected toxicities observed and no additive adverse events reported. Grade 3 or higher adverse events were infrequent, with neutropenia being the most common treatment-emergent adverse event across both the onvansertib combination and standard-of-care arms. The CRDF-004 Phase 2 trial was designed to evaluate the safety, efficacy, and pharmacokinetics of two different doses of onvansertib in combination with FOLFIRI/bevacizumab or FOLFOX/bevacizumab in first-line patients with KRAS- or NRAS-mutated metastatic colorectal cancer (mCRC). The randomized, controlled trial was designed to enroll 110 patients across 6 different arms, and the trial’s endpoints include objective response rate (ORR), progression-free survival (PFS), duration of response, and safety. Onvansertib is a highly specific, oral PLK1 inhibitor advancing toward a registrational trial in first-line RAS-mutated metastatic colorectal cancer (mCRC). In a randomized Phase 2 trial, onvansertib in combination with FOLFIRI/bevacizumab (first-line standard-of-care) demonstrated dose-dependent improvements in overall response rate and progression-free survival compared to standard-of-care alone, building on findings from a prior Phase 2 trial in second-line RAS-mutated mCRC. Based on these results, the Company has selected the 30 mg dose of onvansertib in combination with FOLFIRI/bevacizumab for advancement into a registrational trial in first-line patients with RAS-mutated mCRC. Onvansertib is also being evaluated in multiple other cancers through investigator-initiated studies, including metastatic pancreatic ductal adenocarcinoma, small cell lung cancer, triple-negative breast cancer, and chronic myelomonocytic leukemia.