Notable Labs, Ltd. presented the design for the PPMP-enabled Phase 2 trial with volasertib, in combination with decitabine, in patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) at the American Association for Cancer Research (AACR 2024) being held in San Diego, CA (Poster abstract 5178). Poster Highlights: Guided by a predictive ex vivo test: Bringing the PLK1 inhibitor volasertib back into the clinic for venetoclax-HMA relapsed/refractory acute myeloid leukemia patients: Overview: While prior studies of volasertib demonstrated an approximately 30% complete response/complete response with incomplete count recovery (CR/CRi) rate in de novo AML patients in combination with cytarabine, development was halted in part due to toxicity potentially related to the use of a flat dose, rather than patient-specific, body-surface area (BSA) dosing. Notable Labs provided an updated plan for the design of an open label Phase 2 study, including a dose optimization plan aimed at reducing toxicity while maintaining efficacy and an overview of study objectives and endpoints.

As part of the study, a companion diagnostic assay to predict responders will be co-developed utilizing the Company?s proprietary flow-cytometry-based PPMP. Method: Ex vivo flow cytometry experiments evaluated the treatment of volasertib on 41 primary acute myeloid leukemia (AML) samples collected from peripheral blood or bone marrow. Dose-response profiles consistent with volasertib?s role as a cell cycle inhibitor were observed.

To obtain a preliminary concentration of volasertib for patient stratification, Notable compared the ex vivo resistant blast fractions (leukemic cells surviving ex vivo treatment with volasertib) at several concentrations with the areas under the volasertib dose-response curves (AUCs), assuming that AUCs would correspond most accurately with the clinical responses. Results: The results suggest a strong correlation between volasertib resistant fractions treated with 31.6 and 100 nM of volasertib and AUCs, which could represent a suitable metric to stratify patients into responders and non-responders. These preliminary metrics predict that 32-33% of de novo patients and 25% of R/R AML patients would be predicted to be responders if they were treated with volasertib.