Blocking PLK1 in RAS‑mutated chronic myelomonocytic leukemia
Official title: Targeting PLK1 in RAS mutant chronic myelomonocytic leukemia
Funded at Mayo Clinic Rochester · NIH-11304074 · Data updated 2026-11-12
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 type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Mayo Clinic Rochester NIH-funded |
| Lab location | 1 site (Rochester, United States) |
| Project start | May 1, 2023 |
| Project end | April 30, 2028 |
| Funding year | 2026 |
| Award (this year) | $427,131 |
| NIH project number | 5R01CA272496-04 |
| Project ID | NIH-11304074 on NIH RePORTER |
Who could benefit from this research
✓Could help
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.
✕Less likely to help
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.
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.
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 gone: 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
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Mayo Clinic Rochester
Rochester, United States Active
Researchers
- Principal investigator: Patnaik, Mrinal Shiv — Mayo Clinic Rochester
- Study coordinator: Patnaik, Mrinal Shiv
Related research
Other NIH-funded projects on the same topics.
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Targeted therapies for a blood cancer called CMML (CBL-mutant CMML)
A physician-scientist is testing targeted drugs to treat a hard-to-kill blood cancer called CMML in patients whose cancer has CBL mutations.
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Understanding how CMML develops and becomes aggressive
Looks at blocking overactive MEK/ERK signals and BET protein-driven gene activity to slow or reverse aggressive CMML and lower its chance of turning into AML for people whose leukemia has NRAS and ASXL1 mutations.
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How inflammation changes blood stem cells and drives progression in chronic myelomonocytic leukemia
Looking at whether inflammation changes blood stem cells and speeds disease in adults with CMML.
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Patient-based mouse models to find better treatments for chronic myelomonocytic leukemia
Researchers are using mice implanted with patients' CMML cells to try out new treatment approaches for people with chronic myelomonocytic leukemia.
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Understanding how chronic myelomonocytic leukemia resists targeted therapy
This study is looking at how some people with chronic myelomonocytic leukemia (CMML) might not respond to a treatment called cobimetinib, and it aims to help those patients by figuring out why that happens and finding better ways to treat them.
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Targeting a specific protein to treat a type of blood cancer
This study is looking at a new pill called Onvansertib to see if it can help people with a tough type of blood cancer called chronic myelomonocytic leukemia (CMML) that hasn't responded to other treatments, especially for those with specific gene changes.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.