PURPOSE: Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 
testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. The 
aim of this analysis is to examine the potential of idasanutlin to prolong the 
corrected QT (QTc) interval by evaluating the relationship between plasma 
idasanutlin concentration and QTc interval.
METHOD: Intensive plasma concentration QTc interval data were collected at the 
same timepoints, from three idasanutlin (RO5503781) phase 1 studies in patients 
with solid tumors and AML. QTc data in absolute values and changes from baseline 
(Δ) were analyzed for a potential association with plasma idasanutlin 
concentrations with a linear mixed effect model. Categorical analysis was also 
performed.
RESULTS: A total of 282 patients were exposed to idasanutlin and had at least 
one observation of QTc and idasanutlin plasma concentration. There was no 
apparent increase of QTcF or ΔQTcF in a wide idasanutlin plasma concentration 
range, even at concentrations exceeding the exposure matching the dose adopted 
in the ongoing phase 3 study (300-mg BID). Categorical analysis did not detect a 
potential signal of QT prolongation.
CONCLUSION: The concentration-QTc analysis indicates that idasanutlin does not 
prolong the QT interval within the targeted concentration range currently in 
consideration for clinical development.