Trovagene, a California-based cancer research company, has announced the successful completion of the second dosing cohort in its Phase 1b/2 trial investigating the Onvansertib-decitabine combination for treating acute myeloid leukaemia (AML). This trial aims to assess the efficacy and safety of Onvansertib, a selective oral Polo-like Kinase 1 (PLK1) inhibitor, when used in conjunction with decitabine, a standard treatment for AML.

Onvansertib and decitabine combination progress

Onvansertib, designed for oral administration, boasts a 24-hour half-life and specifically targets the PLK1 enzyme, potentially improving long-term outcomes compared to previous PLK inhibitors used for AML. The trial involves patients who are either ineligible for intensive induction therapy or have relapsed or refractory AML.

The Phase 1b/2 trial included a cohort of three patients treated with Onvansertib at a dose of 18 mg/m², administered orally once daily on days 1-5 of each treatment cycle, in combination with decitabine. Trovagene reported that this regimen was well-tolerated, prompting the Safety Review Committee (SRC) to recommend escalating the Onvansertib dose to 27 mg/m² for future patients.

Expert opinions on the trial

Amer Zeidan, the lead investigator of the trial, expressed optimism about the early results, noting that no dose-limiting toxicities were observed in the initial cohort. He highlighted one patient who had significant reductions in blast counts and transfusion independence, with no major side effects.

Dr. Mark Erlander, Chief Scientific Officer at Trovagene, commented on the promising responses, particularly in the challenging setting of relapsed AML post-allogeneic stem cell transplantation. He emphasized the trial’s focus on enhancing quality of life and extending survival for patients with limited options.

Upcoming phases of the trial

The primary goal of the Phase 1b dose-escalation segment is to determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D). The next phase will involve 32 patients receiving the MTD or RP2D to evaluate the preliminary antitumor activity and continue assessing the safety and tolerability of the Onvansertib-decitabine combination.

What’s next for Trovagene’s AML research

Trovagene remains committed to advancing its AML research and will continue to explore the Onvansertib-decitabine combination in future trials. The company aims to identify the optimal dose for broader application and further develop therapies for hematologic cancers.

  Acute myeloid leukemia, Amer Zeidan, Decitabine, Dr. Mark Erlander, Oncology, Onvansertib, Trovagene, USA