Trovagene, a California-based cancer research company, said that it has wrapped up the second dosing cohort of the Onvansertib-decitabine combination, in a phase 1b/2 acute myeloid leukemia trial.
Onvansertib is said to be a highly-selective oral Polo-like Kinase 1 (PLK1) inhibitor. Designed to be orally administered, Onvansertib has a 24-hour drug half-life.
According to Trovagene, the specific targeting of the PLK1 enzyme and enabling a flexible dose and dosing schedule can greatly improve on the long-term outcome seen in past studies with a PLK inhibitor in acute myeloid leukemia.
Decitabine, on the other hand, is standard-of-care treatment for acute myeloid leukemia.
The phase 1b/2 acute myeloid leukemia trial by Trovagene is being held in patients who are not eligible for intensive induction therapy or whose condition is relapsed or refractory.
Trovagene said that it had completed treatment of all the three patients in the investigational cohort with Onvansertib at 18mg/m2, orally administered, daily once, on days 1-5 of the treatment cycle, along with decitabine. The Onvansertib decitabine combination was well tolerated, said the US cancer research company.
Trovagene revealed that the Safety Review Committee (SRC) has suggested escalating the dosage of Onvansertib to 27mg/m2 in combination with decitabine.
Commenting on the phase 1b/2 acute myeloid leukemia trial of the Onvansertib decitabine combination, Amer Zeidan, its lead investigator, said: “While we are still early in the trial, we continue to be excited by what we are seeing so far from both a safety and efficacy standpoint.
“We did not see any dose limiting toxicities and treatment has been well tolerated in the cohort of three patients who received Onvansertib at 18 mg/m2 in combination with decitabine. One of our patients is about to start his 6th cycle of combination therapy, with significant reductions in his blast counts, transfusion independence, and no significant side effects.
The primary objective of the phase 1b dose-escalation segment of the acute myeloid leukemia trial is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), through a conventional 3+3 design.
In Phase 2, 32 patients will be subjected to the MTD or RP2D to assess preliminary antitumor activity and to continue to study the safety and tolerability of Onvansertib combined with standard-of-care chemotherapy.
Dr. Mark Erlander – Chief Scientific Officer of Trovagene, commenting on the phase 1b/2 acute myeloid leukemia trial, said: “This is a very gratifying response to see, especially in the incurable setting of relapsed AML post allogeneic stem cell transplantation, where the focus is on quality of life improvement in addition to prolonging survival.”
“We are pleased with the progress we are making to identify our maximum tolerated dose and recommended Phase 2 dose for the continuation segment of our AML trial, as well as for use in other trials that we may do in the future in hematologic (leukemias/lymphomas) cancers.”
Keep following www.PharmaNewsDaily.com for more updates on the acute myeloid leukemia trials by the US cancer research company Trovagene for the Onvansertib decitabine combination.