Cardiff Oncology (NASDAQ:CRDF) outlined a management transition and provided an updated clinical data readout for onvansertib during a company conference call focused on its ongoing Phase II CRDF-004 trial in first-line RAS-mutated metastatic colorectal cancer (mCRC).
Leadership transition framed as positioning for late-stage development
Interim CEO Mani Mohindru said the board initiated a leadership transition “aimed at positioning the company optimally for late-stage development” as Cardiff moves toward finalizing and executing a registrational plan for onvansertib in first-line RAS-mutated mCRC. Mohindru, a Cardiff board member since 2021, said the change reflects evolving management and financial needs as the company prepares for its next phase of growth.
Trial overview: dose-finding in combination with standard regimens
The data update centered on CRDF-004, a company-sponsored Phase II dose-finding study evaluating onvansertib—an oral PLK1 inhibitor—in combination with standard first-line mCRC regimens in patients whose tumors harbor RAS mutations. Patients were randomized to receive either 20 mg or 30 mg of onvansertib alongside one of two backbones: FOLFIRI plus bevacizumab or FOLFOX plus bevacizumab. Control patients received standard-of-care therapy alone.
Mohindru said the study is designed to identify the lowest effective dose while assessing safety, efficacy, and pharmacokinetics (PK) in the combination setting.
Updated efficacy: benefit most consistent with FOLFIRI plus bevacizumab
In an intent-to-treat analysis, Cardiff reported what it described as dose-dependent benefits across multiple efficacy measures, most notably in patients treated with onvansertib plus FOLFIRI and bevacizumab compared with standard-of-care regimens. Mohindru said similar consistent, dose-dependent benefit has not been observed so far in the onvansertib plus FOLFOX and bevacizumab cohorts.
He highlighted that the updated first-line FOLFIRI/bevacizumab results align with prior positive findings from a second-line Phase II study in bevacizumab-naïve mCRC patients that also used a FOLFIRI backbone—results that were published in the Journal of Clinical Oncology and supported the company’s move to the first-line setting following consultation with the FDA.
From the table referenced in the press release, Mohindru said the 30 mg dose of onvansertib combined with FOLFIRI and bevacizumab produced a confirmed objective response rate (ORR) of 72.2%, compared with 43.2% for the combined standard-of-care regimens and 42.1% for FOLFIRI plus bevacizumab alone. He added that median progression-free survival (PFS) has not yet been reached in either onvansertib FOLFIRI arm, while the standard-of-care regimens had a median PFS of about 11 months, which he said aligns with published data.
Mohindru also said the 30 mg arm achieved statistical significance for PFS versus standard of care despite the small sample size, and he cited a PFS hazard ratio of 0.37 for 30 mg onvansertib plus FOLFIRI/bevacizumab versus the combined standard-of-care arms. He cautioned that the dose-selection trial was not powered to detect differences in secondary endpoints such as PFS or duration of response, but said the company nevertheless observed dose-dependent durability measures favoring the higher dose.
Dose selection and registrational plans
Based on what Mohindru called the “totality of the data,” Cardiff selected 30 mg onvansertib with FOLFIRI plus bevacizumab to advance into a registrational study in first-line RAS-mutated mCRC. The company expects to initiate a registrational program later in 2026, with a protocol that will likely compare onvansertib plus FOLFIRI/bevacizumab to both standard-of-care regimens (FOLFIRI/bevacizumab and FOLFOX/bevacizumab), subject to FDA feedback.
In Q&A, Mohindru said the company is not yet in a position to discuss Phase III sample size or powering assumptions, stating those decisions will be developed with regulators. He also explained why the company is considering including both chemotherapy backbones in the control arm: both regimens are used in first line, and physicians and regulators may prefer comparative data against both, particularly since Cardiff believes the FOLFIRI/onvansertib combination appears better than both standard approaches.
Safety, data maturity, and upcoming milestones
Management said safety and tolerability remained favorable, with no unexpected toxicities or additive adverse events reported. Grade 3 or higher adverse events were described as infrequent, with neutropenia cited as among the most common treatment-emergent events across arms.
Several analysts pressed for additional details—such as baseline characteristics, depth of response over time, time to response, discontinuation rates, and separate results for blinded independent central review (BICR) versus investigator assessment—but management largely deferred, citing small numbers and an ongoing study. Mohindru said the company combined BICR and investigator assessments to make the results more meaningful given limited events.
Cardiff expects to provide a more mature CRDF-004 dataset before the end of the first half of 2026, potentially at a medical meeting or similar event. By that time, the company also anticipates receiving FDA feedback on its registration plan. Mohindru added that the company is open to strategic discussions, including partnerships, and said some discussions had already begun under prior leadership.
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.
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