Tolero Pharmaceuticals has enrolled the first patient in its Phase Ib/II Zella 102 trial.
The trial will examine alvocidib in combination with decitabine for the treatment of myelodysplastic syndromes (MDS).
As part of the open-label, dose-escalation study, the safety and preliminary clinical activity of alvocidib will be investigated when administered after decitabine in MDS patients.
The trial is expected to enrol around 49 patients and will be conducted at several sites in the US.
In Phase Ib of the trial, three to six patients will be enrolled in each group. Escalation of the alvocidib dose will be carried out, with sequential groups of three patients treated with incrementally higher doses of alvocidib until a dose-limiting toxicity (DLT) is observed and the MTD is established.
Following the identification of the MTD, or preliminary recommended Phase II dose (RP2D), the trial will progress to Phase II.
In Phase II, up to 15 eligible patients will be included and treated with the RP2D identified in the Phase Ib study, and ten patients will be enrolled to bring the total enrolment to 25 patients.
The primary endpoint of the Phase Ib portion is to determine the incidence of dose-limiting toxicities and treatment emergent adverse events over 28 days, while the primary objective of the Phase II portion is to determine the objective response rate.
Tolero Pharmaceuticals CEO David Bearss said: “We hypothesise that downregulation of MCL-1 via CDK9 inhibition following decitabine exposure may result in enhanced antileukemic activity.
“We believe that there are some patients with MDS that may have disease dependent on MCL-1.
“This milestone supports our commitment to understanding the potential of alvocidib in this patient population.”
MDS is a type of cancer that usually occurs when cells in the bone marrow are abnormal, thereby leading to the production of defective blood cells that often die earlier than normal cells.