Onvansertib Receives FDA Orphan Drug Designation for CMML

Onvansertib has received orphan drug designation from the US Food and Drug Administration (FDA) for the treatment of chronic myelomonocytic leukemia (CMML), supporting further clinical development of the investigational PLK1 inhibitor in this rare hematologic malignancy.¹

The FDA designation applies to therapies intended to treat rare diseases affecting fewer than 200,000 people in the United States. Potential benefits include tax credits for qualified clinical trials, exemptions from certain FDA user fees, and up to 7 years of market exclusivity following regulatory approval.

“Receiving [o]rphan [d]rug [d]esignation for onvansertib in CMML further validates the therapeutic potential of PLK1 inhibition in cancers with significant unmet need and adds to the growing body of evidence supporting this mechanism across both solid tumors and hematologic malignancies,” Mani Mohindru, PhD, president and CEO of Cardiff Oncology, stated in a news release. “We believe this designation highlights the broader clinical opportunity for onvansertib as a monotherapy as we continue advancing therapies for patients across cancers where new therapeutic approaches are urgently needed.”

About Onvansertib and Preliminary Findings

Onvansertib is an oral, selective inhibitor of PLK1, a protein involved in cell-cycle regulation. The therapeutic rationale for PLK1 inhibition in CMML includes the role of RAS-pathway alterations in disease biology. Approximately 40% to 50% of patients with myeloproliferative CMML harbor RAS-pathway mutations, which are associated with more aggressive disease.²

The agent is being evaluated in a phase 1 investigator-initiated study (NCT05549661) in patients with relapsed or refractory CMML.³ Findings presented at the 2025 American Society of Hematology Annual Meeting indicated that monotherapy was relatively well tolerated and demonstrated preliminary clinical activity in patients with the myeloproliferative subtype of CMML. Approximately 40% of patients with myeloproliferative CMML in the dose-ranging study demonstrated preliminary efficacy. Specifically, 3 patients (38%) experienced clinical benefits, with 1 patient each achieving a 100% platelet response, normalization of an elevated white blood cell count from a baseline exceeding 50 × 10⁹/L, and a spleen response.

An additional patient (12.5%) achieved an optimal bone marrow response, with blasts decreasing from 8% to 2%. This response facilitated the patient's transition to allogeneic hematopoietic stem cell transplantation. Three other patients (38%) experienced stable disease.

Next Steps in Development

Onvansertib is being evaluated across several cancer types through company-sponsored and investigator-initiated studies. In addition to CMML, the investigational drug is being studied in metastatic pancreatic ductal adenocarcinoma, small cell lung cancer, and triple-negative breast cancer.

The company is also advancing onvansertib for RAS-mutated metastatic colorectal cancer. Its broader development program reflects continued investigation of PLK1 inhibition across solid tumors and hematologic malignancies. Additional clinical data will be needed to establish its safety and efficacy and clarify its potential role in treating patients with CMML.

REFERENCES

1. Cardiff Oncology Receives FDA Orphan Drug Designation for Onvansertib in Chronic Myelomonocytic Leukemia. News release. Cardiff Oncology. October 21, 2026. Accessed October 22, 2026. https://tinyurl.com/4w9fz4sr

2. Montalban-Bravo G, Loghavi S, Li Z, et al. Landscape and clinicopathologic features of RAS pathway mutations in chronic myelomonocytic leukemia. Blood Adv. 2025;9(19):5105-5117. doi:10.1182/bloodadvances.2025016529

3. Onvansertib for the Treatment of Recurrent or Refractory Chronic Myelomonocytic Leukemia and Myelodysplastic Syndrome/​MPN Overlap Neoplasms. ClinicalTrials.gov. Updated June 22, 2026. Accessed October 22, 2026.