Cardiff Oncology (NASDAQ:CRDF) used an appearance at Oppenheimer’s 36th Annual Healthcare Conference to highlight updated clinical results and its development plans for onvansertib, an oral, highly selective polo-like kinase 1 (PLK1) inhibitor being studied in RAS-mutated metastatic colorectal cancer (mCRC) and other RAS-driven cancers.
Focus on first-line RAS-mutated metastatic colorectal cancer
Chief Executive Officer Mani Mohindru described first-line RAS-mutated mCRC as a large market with high unmet need, noting that standard treatment has remained largely unchanged for decades and that there is no drug “truly approved” for the RAS-mutated mCRC population. Mohindru said roughly half of metastatic colorectal cancer patients carry KRAS or NRAS mutations, and he emphasized that many emerging approaches are mutation-specific, leaving a substantial portion of RAS-mutated patients without targeted options.
Phase II results: response rate and early durability signals
The company’s lead dataset discussed during the presentation came from an ongoing randomized Phase II study in the frontline setting. Mohindru said 110 patients with unresectable metastatic disease and KRAS or NRAS mutations were randomized across multiple arms to compare standard-of-care regimens versus standard-of-care plus onvansertib at two doses (20 mg and 30 mg). Onvansertib was dosed on days 1–5 and 15–19 of a 28-day cycle alongside chemotherapy and bevacizumab.
Cardiff highlighted results from the FOLFIRI plus bevacizumab backbone:
- Confirmed overall response rate (ORR): Mohindru said the 30 mg onvansertib + FOLFIRI + bevacizumab arm produced a confirmed ORR of 72.2%, compared with 43.2% for the combined standard-of-care group and 42.1% for the FOLFIRI + bevacizumab standard-of-care arm.
- Depth of response: He said responses were deeper in onvansertib-treated patients compared with standard of care.
- Progression-free survival (PFS): Mohindru said median PFS was about 11 months for FOLFIRI + bevacizumab, while median PFS had not been reached in the 20 mg or 30 mg onvansertib arms at the time of the update, with follow-up continuing.
- Hazard ratios and statistical testing: He said hazard ratios showed favorable trends for the onvansertib arms versus control. He also said that when comparing the 30 mg arm to the combined standard-of-care group, the company “was even able to reach statistical significance” with a p-value less than 0.05.
Mohindru added that there were “a couple of patients” in the 30 mg arm who went on to curative surgery. He also characterized the safety profile as “completely unremarkable,” stating that there were no additive toxicities apparent when onvansertib was added to chemotherapy and bevacizumab.
How earlier second-line findings informed frontline development
Mohindru also reviewed a prior Phase Ib/II study in second-line metastatic colorectal cancer that evaluated onvansertib in combination with FOLFIRI and bevacizumab. He described a post-hoc analysis suggesting outcomes differed based on prior exposure to bevacizumab:
- In bevacizumab-naïve second-line patients, he said the study showed a 73% overall response rate and a median PFS of 15 months.
- In patients previously exposed to bevacizumab, he said the overall response rate was 16% and median PFS was 7.8 months.
He said these observations, along with internal preclinical work, supported the hypothesis of synergy between onvansertib and bevacizumab, potentially connected to anti-angiogenic effects. He also cited synthetic lethality in RAS-mutant tumors and synergy with chemotherapy through interference with DNA repair mechanisms as part of the rationale for combining a PLK1 inhibitor with standard regimens.
Regulatory plans and potential registrational study design
Mohindru said Cardiff expects to finalize its path to registration in frontline RAS-mutated mCRC after discussions with U.S. regulators, adding that the company believes the 30 mg dose is the best candidate to take forward. He said the company aims to provide regulatory feedback and a fuller plan “within this first half of this year,” though later in the presentation he also said it hopes “within first half of 2026” to share more data and provide regulatory feedback on next steps.
As a working concept pending FDA discussions, Mohindru outlined a potential Phase III approach evaluating 30 mg onvansertib with FOLFIRI and bevacizumab against current standard-of-care regimens based on investigator’s choice. He said the company is considering whether accelerated approval or full approval could potentially be built into a single study and described ORR and PFS as primary endpoints, with additional durability measures as secondary endpoints. He said the trial would be global.
Partner support, other indications, and cash runway
Mohindru said Pfizer has served as a contract research organization partner for Cardiff’s trial execution through Pfizer’s Breakthrough Growth Initiative and has made a $15 million investment. He emphasized that Cardiff retains full rights to the onvansertib program, while noting obligations to provide data in a timely manner.
Beyond colorectal cancer, Mohindru pointed to investigator-initiated studies exploring onvansertib in other settings, including chronic myelomonocytic leukemia (CMML). He said an investigator-initiated study at Mayo Clinic (Rochester) showed single-agent activity in CMML and that data were presented at ASH in December 2023. He described CMML as a disease with poor prognosis and no approved drugs in the relapsed/refractory setting, and noted orphan designation.
On the financial side, Mohindru said the company reported $58.3 million in cash and cash equivalents, which he said should fund operations into Q1 2027. In Q&A, he clarified that this runway estimate does not include any significant investment in a Phase III trial, though it does include the ongoing study and other company activities.
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.
