Cardiff Oncology announced on October 21, 2026, that the U.S. Food and Drug Administration has granted Orphan Drug Designation to onvansertib for the treatment of patients with chronic myelomonocytic leukemia (CMML). Onvansertib is a highly specific, oral inhibitor of polo-like kinase 1 (PLK1) currently under evaluation across multiple tumor types, including a Phase 1 investigator-initiated study in relapsed/refractory CMML.
The designation follows early clinical data presented at the 2025 American Society of Hematology Annual Meeting, in which onvansertib as a monotherapy demonstrated preliminary efficacy in approximately 40% of myeloproliferative CMML patients enrolled in a dose-ranging trial. The dataset is small, and formal efficacy endpoints and patient numbers have not yet been fully reported.
Key finding
The FDA granted Orphan Drug Designation to onvansertib for CMML based on preliminary monotherapy activity in a small dose-ranging trial, though the study remains early-stage and definitive efficacy data have not yet been established.
Study Design
| Trial | Phase 1 investigator-initiated study |
|---|---|
| Population | Patients with relapsed/refractory CMML |
| Treatment | Onvansertib monotherapy (dose-ranging) |
The Phase 1 study is investigator-initiated and was designed as a dose-ranging trial in relapsed/refractory CMML. Primary endpoint, key secondary endpoints, and full enrollment figures were not disclosed in the source material. Data from the trial were presented at the 2025 ASH Annual Meeting.
Results and Safety
As reported at the 2025 ASH Annual Meeting, onvansertib demonstrated preliminary efficacy in approximately 40% of myeloproliferative CMML patients enrolled in the dose-ranging trial. Three patients (38%) experienced clinical benefit, with responses consisting of one patient achieving a 100% platelet response, one achieving normalization of white blood cell count from a baseline greater than 50 × 10⁹/L, and one achieving a spleen response. One additional patient (12.5%) achieved an optimal marrow response, with bone marrow blast reduction from 8% to 2%, which facilitated eligibility for allogeneic hematopoietic stem cell transplant. Three patients (38%) experienced stable disease.
Cardiff Oncology characterized onvansertib as relatively well-tolerated as a monotherapy in this population. Detailed safety data, including specific adverse event rates and grades, were not disclosed in the announcement.
Clinical Context
CMML is a rare and difficult-to-treat hematologic malignancy with limited approved treatment options. According to Cardiff Oncology, 40–50% of patients with myeloproliferative CMML harbor RAS-pathway mutations, which are associated with more aggressive disease. The prevalence of RAS-pathway alterations in this population aligns with onvansertib’s proposed mechanism, as PLK1 inhibition has shown activity in RAS-mutated cancers across both solid tumors and hematologic malignancies.
Orphan Drug Designation confers potential benefits including tax credits for qualified clinical trials, exemption from certain FDA user fees, and up to seven years of market exclusivity upon regulatory approval. The designation does not alter standard regulatory requirements or the approval pathway. Whether Cardiff Oncology plans to advance onvansertib into a registrational study specifically in CMML has not been announced; the company’s stated near-term registrational priority remains first-line RAS-mutated metastatic colorectal cancer.
Sources
- GlobeNewswire / Cardiff Oncology. “Cardiff Oncology Receives FDA Orphan Drug Designation for Onvansertib in Chronic Myelomonocytic Leukemia.” Press release. October 21, 2026. View source.
