Onvansertib Demonstrates Single-Agent Activity in CMML: Cardiff Oncology's Phase 1 ASH 2025 Data

Cardiff Oncology, Inc. (CRDF) has unveiled compelling preliminary efficacy data for onvansertib, a novel oral PLK1 inhibitor, in treating patients with treatment-resistant chronic myelomonocytic leukemia at the 67th American Society of Hematology Annual Meeting on December 8, 2025. The poster presentation, spearheaded by Dr. Mrinal Patnaik from Mayo Clinic, showcases progress in addressing this challenging hematologic disorder.

Understanding the Clinical Challenge

Chronic myelomonocytic leukemia represents a rare blood malignancy that blurs the line between two disease categories. It exhibits characteristics of both myelodysplastic syndromes—marked by defective blood cell production—and myeloproliferative neoplasms with excessive cell growth. This dual nature creates a particularly difficult clinical scenario, as patients face declining blood cell counts alongside elevated transformation risk to acute myeloid leukemia. Current treatment options remain limited, making novel therapeutic approaches critically important.

Trial Design and Safety Profile

The Phase 1 dose escalation study enrolled nine patients receiving onvansertib as monotherapy. The drug, which selectively targets Polo-like kinase 1 (PLK1)—a critical regulator of cell division—demonstrated a manageable safety profile. Most treatment-emergent adverse events were reportedly well-tolerated, with no major safety signals emerging from the limited patient cohort.

Efficacy Signals and Mechanism

Approximately 40% of patients showed preliminary efficacy, a notable finding in this difficult-to-treat population. One patient achieved an optimal marrow response at the 9 mg/m² dose level, validating onvansertib’s single-agent potential in hematologic malignancies. These results complement earlier observations in small cell lung cancer, suggesting PLK1 inhibition may overcome resistance mechanisms across both hematologic and solid tumor indications.

Broader Development Strategy

While Cardiff Oncology has decided not to pursue further development in CMML at this time, the company’s pipeline strategy remains ambitious. The primary focus centers on combining PLK1 inhibition with standard-of-care treatments in RAS-mutated metastatic colorectal cancer. Additionally, investigator-initiated trials are underway exploring this approach in metastatic pancreatic ductal adenocarcinoma, small cell lung cancer, and triple-negative breast cancer.

Market Response

CRDF stock responded positively to the update, closing the previous session at $2.34, representing a 10.90% gain, with further appreciation to $2.35 in after-hours trading. Over the trailing twelve months, the stock has ranged between $1.90 and $5.64, reflecting market sentiment around the company’s clinical progress and pipeline potential.