First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13).

•The maximum tolerated dose and recommended phase 2 dose of PQR309 is 80 mg orally OD.•Pharmacodynamics shows phosphatidylinositol-3-kinase (PI3K)–mammalian target of rapamycin (mTOR)–S6 pathway inhibition in paired tumour biopsies.•Pathway inhibition is more pronounced in patients with tumour shrinkage.•Activity was observed in patients with and without PI3K pathway dysregulation.•Tumour-associated immune infiltrates were not affected by PI3K/mTOR inhibition.