Pharmacodynamics
tumor, tumors
TUMOR, TUMORS
Met-EF1α accumulation in tumors was observed at 7 mg once daily and tended to increase up to 35 mg once daily in a dose-dependent manner in line with the observed increase of exposure (Met-EF1α/protein levels in tumor on cycle 2, day 1 (individual patient dot plot). Open symbols show the pretreatment Met-EF1α levels, and the corresponding closed symbols show cycle 2, day 1 Met-EF1α levels for individual patients for the doses of 7, 12, 20, 35, 60, and 80 mg. The dashed line shows the target Met-EF1α level of 125 μg/mg protein expected to be correlated with efficacy. Met-EF1α, methionylated elongation factor 1α.At 12 mg once daily and higher, a low and variable pharmacodynamic response was detected in WBCs from cycle 1, day 15 onward; no obvious dose correlation was observed.On the basis of the observed safety, pharmacokinetic, and pharmacodynamic data, the SMC suggested a dose of 35 mg once daily as the RP2D for M8891 monotherapy.