Blocking PLK1 in RAS‑mutated chronic myelomonocytic leukemia

Targeting PLK1 in RAS mutant chronic myelomonocytic leukemia

NIH-funded research Mayo Clinic Rochester · NIH-11304074

People with relapsed or refractory proliferative CMML that has RAS pathway mutations will receive an oral drug called onvansertib that blocks the cell‑division protein PLK1 to look for safety and early signs of benefit.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionMayo Clinic Rochester NIH-funded
Lab location1 site (Rochester, United States)
Project IDNIH-11304074 on NIH RePORTER

What this research studies

This is a Phase 1, early‑phase trial testing onvansertib, an oral PLK1 inhibitor, in patients with proliferative CMML that carry RAS pathway mutations. The study uses a BOIN (Bayesian Optimal Interval) dose‑finding design to identify safe dose levels and to look for preliminary anti‑leukemia activity. Participants will have regular clinic visits for drug dosing, blood tests, and bone marrow sampling for safety checks and laboratory studies of how the drug affects cancer cells. The protocol may explore combinations with hypomethylating agents and will collect samples to look for biomarkers that predict response.

Who could benefit from this research

Good fit: Adults with relapsed or refractory proliferative CMML who have RAS pathway mutations (for example NRAS or KRAS) and who meet the study’s health and lab criteria are the intended participants.

Not a fit: Patients without RAS pathway mutations or those with the dysplastic CMML subtype (and some with poor organ function or other active illnesses) are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this could become a targeted treatment option that slows disease progression and offers benefit for people with RAS‑mutant pCMML.

How similar studies have performed: Laboratory studies and early AML trials of PLK1 inhibitors have shown activity and increased sensitivity in RAS‑mutant cells, but using onvansertib specifically in RAS‑mutant pCMML is a novel, early‑phase approach.

Where this research is happening

Rochester, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.