Table 1.

MTD, effect marker–based dose, and clinical dose of selected drugs for which clinical development programs used effect markers

CompoundMTDEffect marker–based doseClinical dose
CetuximabNot reached200 mg/m2 q1w250 mg/m2 q1w as maintenance dose (initial dose = 400 mg/m2)
PembrolizumabNot reached up to 10 mg/kg q2w2 mg/kg q3w2 mg/kg q3w
IdelalisibNot reached up to 350 mg twice a day150 mg twice a day150 mg twice a day
Decitabine1,500–2,000/mg/m2 over 1–3 days15–20 mg/m2/d over 10 days20 mg/m2/d over 5 days
VismodegibNot reached up to 540 mg/d150 mg/d150 mg/d
Crizotinib250 mg twice a day250 mg twice a day; pharmacodynamic marker helped in target population selection250 mg twice a day (Alk-positive patients)
GalunisertibNot able to determine MTD due to potential cardiovascular DLT160–360 mg/d with intermittent dosing (2 weeks on and 2 weeks off)Not approved yet; pharmacokinetic–pharmacodynamic model–based intermittent dosing enabled clinical development

Abbreviations: q1w, every week; q2w, every 2 weeks; q3w, every 3 weeks.