ASH 2020 | Phase I/Ib trial of talazoparib plus gemtuzumab ozogamicin in R/R AML

At our Institute, we have initiated an investigator-initiated clinical trial, investigating the possibility of combining two novel classes of agents for AML therapy. This Phase I/Ib study is evaluating the safety and tolerability as well as preliminary efficacy of gemtuzumab ozogamicin, the CD33 antibody-drug conjugate in combination with PARP inhibitor talazoparib.

Now PARP inhibitors have been approved for the treatment of solid tumor malignancies, specifically breast and ovarian cancers associated with BRCA mutations. These PARP inhibitors function by targeting a DNA repair pathway, which is compromised in patients with BRCA mutations, thus initiating a cascade leading to cell death and that sensitive ovarian and breast cancer cells.

We have determined in our laboratory here at Roswell Park that the combination of PARP inhibitor, talazoparib and gemtuzumab results in synergistic anti-leukemic effects by induction initially of cytotoxic cell death, followed by impairment of DNA repair. This trial aims to enroll 20 patients with relapsed and refractory AML, and escalate the dose of the talazoparib dose as a cohort with the fixed-dose of gemtuzumab monotherapy and the regimen previously approved for relapsed patients. Today, we have enrolled two to three patients that are on the first dose cohort and we’re evaluating the initial safety and tolerability signals before moving forward to additional dose cohort.