Cardiff Oncology (NASDAQ:CRDF) said updated interim data from its randomized Phase 2 CRDF-004 trial support advancing onvansertib into a pivotal Phase 3 study for first-line RAS-mutated metastatic colorectal cancer.
During a conference call following a presentation at the American Society of Clinical Oncology meeting, President and Chief Executive Officer Mani Mohindru said the company believes onvansertib, a polo-like kinase 1, or PLK1, inhibitor, has “practice-changing potential” when combined with FOLFIRI and bevacizumab in this patient population.
As of the March 18, 2026, data cutoff, median progression-free survival had not been reached in the 30 mg onvansertib plus FOLFIRI-bevacizumab arm. Cardiff said some patients remained on treatment beyond 15 to 18 months.
Phase 2 Trial Supports Selected Dose and Regimen
CRDF-004 is a dose-finding, randomized controlled Phase 2 trial in first-line metastatic colorectal cancer patients with KRAS or NRAS mutations. The trial tested two doses of onvansertib, 20 mg and 30 mg, in combination with either FOLFIRI-bevacizumab or FOLFOX-bevacizumab, compared with the chemotherapy-bevacizumab backbones alone.
Mohindru said the trial’s goal was to identify a dose and regimen for further development. Cardiff selected 30 mg onvansertib plus FOLFIRI-bevacizumab for its planned Phase 3 trial.
The company said the 20 mg onvansertib plus FOLFIRI-bevacizumab arm showed a 44.4% ORR, while the 30 mg arm demonstrated greater activity. Mohindru said internal analyses showed a dose-exposure-response relationship and that Cardiff views 20 mg as active, though 30 mg provides the efficacy profile the company plans to take forward.
For progression-free survival, Cardiff reported that the combined onvansertib plus FOLFIRI-bevacizumab arms had a hazard ratio of 0.44 by independent review compared with combined standard-of-care regimens, with median PFS not reached in the onvansertib arm versus 11.04 months in the control arm. Investigator-assessed results showed a hazard ratio of 0.53, with median PFS not reached versus 10.97 months for control.
For the selected 30 mg onvansertib plus FOLFIRI-bevacizumab regimen, Cardiff reported hazard ratios of 0.55 by independent review and 0.57 by investigator assessment. The company said the trial was not powered for PFS, but described the trends as encouraging.
Safety Profile Described as Tolerable
Cardiff said adding onvansertib to FOLFIRI-bevacizumab or FOLFOX-bevacizumab did not introduce unexpected overlapping or new toxicities. The most common adverse events were described as consistent with the known profiles of the chemotherapy and bevacizumab regimens, and grade 3 or higher events were comparable across arms.
Mohindru said no unusual or unexpected onvansertib-specific safety signals were identified. He added that the tolerability profile supports moving the drug into a Phase 3 program in the first-line setting.
The company also said the FOLFOX-bevacizumab combinations did not produce a meaningful improvement in ORR or PFS versus FOLFOX-bevacizumab alone. Mohindru said Cardiff believes mechanistic differences may explain why onvansertib appears to pair better with FOLFIRI than FOLFOX.
External Oncologists Discuss Clinical Context
Heinz-Josef Lenz, Associate Director for Clinical Research at USC Norris Comprehensive Cancer Center, said he has been involved with onvansertib since early development and described the drug as “very well-tolerated,” noting that it is administered orally for five days in a two-week cycle.
Lenz said the randomized Phase 2 trial confirmed a clinical signal seen in Cardiff’s earlier Phase 1b/2 study, particularly the apparent synergy between onvansertib, FOLFIRI and bevacizumab.
Josep Tabernero, Director of the Vall d’Hebron Institute of Oncology, said he supports evaluating onvansertib with FOLFIRI and bevacizumab in first-line KRAS- and NRAS-mutated metastatic colorectal cancer. He said the data presented at ASCO were “really very exciting” and described the 72% response rate as “amazing” in this setting.
In response to analyst questions, both Lenz and Tabernero said they did not see evidence that the benefit was limited to a specific KRAS or NRAS mutation subtype. Lenz said onvansertib acts downstream of individual RAS mutations rather than binding to a specific allele.
Phase 3 Trial Planned
Cardiff said it completed an end-of-Phase 2 meeting with the U.S. Food and Drug Administration during the second quarter of 2026 and aligned on a registrational path. The planned Phase 3 trial, CRDF-005, is expected to evaluate 30 mg onvansertib plus FOLFIRI-bevacizumab versus FOLFIRI-bevacizumab alone in a global randomized study.
The proposed trial is expected to enroll approximately 640 patients and have dual primary endpoints: ORR to support potential accelerated approval and PFS to support full approval. Secondary endpoints include duration of response and overall survival. Mohindru said Cardiff is still awaiting feedback from the European Medicines Agency.
During the Q&A session, Mohindru said FDA guidance indicated the trial would likely need to be fully enrolled before an accelerated approval submission based on ORR, though not necessarily fully read out for PFS.
He also said that, pending funding, Cardiff expects to begin Phase 3 initiation-related activities late this year or early next year.
License Dispute Addressed
Asked about Cardiff’s dispute with Nerviano, Mohindru said the company sought legal intervention after efforts to resolve the matter outside the courts. He said the dispute relates to inventorship in Cardiff’s patents and commercially reasonable efforts under the license agreement.
Mohindru said Cardiff believes the license agreement remains active and that the dispute does not affect the company’s development plans. “From our perspective, it is business as usual,” he said.
About Cardiff Oncology (NASDAQ:CRDF)
Cardiff Oncology, Inc is a clinical-stage biopharmaceutical company headquartered in Cambridge, Massachusetts. The company is dedicated to the discovery, development and commercialization of novel small-molecule therapies designed to modulate the tumor microenvironment and enhance antitumor immune responses. By focusing on unique immuno-oncology targets, Cardiff seeks to address resistance pathways that limit the effectiveness of existing cancer treatments.
Cardiff’s pipeline comprises several small-molecule immunomodulators in various stages of preclinical and clinical development.
