Aptose Biosciences Inc (APTO)

[dcaf7]

Interesting recent paper, “Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia” with Daver as first author. It shows modified composite complete response (mCRc) rate of 75% in Flt3mut patients in Phase 1b study. mCR includes complete response [CR], CR with incomplete blood count recovery, CR with incomplete platelet recovery and morphologic leukemia-free state. Not sure how it is related to Tusp data. If you count only CR+CRp, CR rate would be 36%. I like that they used additional approach to estimate how drug works, it is to measure variant allelic frequency (VAF), for example for Flt3. They define a molecular response (MR) when VAF < 10-2. In this study, 60% of patients reached MR, and mOS for patients with both mCRs and MRs was longer than for patients with mCRs. 12% of patients reached undetectable levels of Flt3-ITD (VAF< 10-6) which is remarkable.
They also noticed that “of 31 patients with FLT3mut and baseline next-generation sequencing data, 17 had concomitant mutations in DNMT3A, 13 in NPM1, nine in both DNMT3A and NPM1, and eight in IDH1/2; mCRc rates were generally consistent regardless of the presence or absence of comutations”.
Other takeaway from this paper is that a dose escalation part of the study was short, 400 mg of Venetoclax and only 2 different doses of Gilt. I guess, they completed it before Project Optimus was introduced.
https://ascopubs.org/doi/full/10.1200/JCO.22.00602