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

Eunice Wang, MD, Roswell Park Comprehensive Cancer Center, Buffalo, NY shares the design of a Phase I study (NCT04207190) of talazoparib (tala), a PARP inhibitor, in combination with gemtuzumab ozogamicin (GO) in relapsed/refractory (R/R) acute myeloid leukemia (AML). PARP inhibition through tala inhibits base excision repair pathways, which may improve the efficacy of GO, an anti-CD33 antibody-drug conjugate. The study will compare tala+GO to GO as a single agent, to determine the safety and overall response rate of combination treatment in CD33-positive AML. Dose expansion will follow after the determination of the recommended Phase II dose. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.

Transcript (edited for clarity)

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...

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.

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Disclosures

Dr Eunice Wang, MD, has participated in advisory boards for AbbVie, Astellas, BMS/Celgene, Genentech, Jazz, Kite Pharmaceuticals, Macrogenics, Novartis, Pfizer, PTC Therapeutics, Stemline and Takeda; has fulfilled speaker roles for Stemline, Pfizer and Dava Oncology; and has been a member of data monitoring committees for AbbVie and Rafael Pharmaceuticals.

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