A phase 1 first-in-human (FIH) dose-escalation (DE) study of the oral dual PI3K/mTOR inhibitor PQR309 in patients (pts) with advanced solid tumors: Final DE results.

2592 Background: PQR309 is a novel, orally bioavailable, balanced pan-PI3K, mTORC1 and mTORC2 inhibitor. Methods: An accelerated 3+3 DE, open label Phase 1 trial of continuous once daily (OD) PQR309 to evaluate safety, pharmacokinetics (PK) and pharmacodynamics (PD) in pts with advanced solid tumours was performed. Pts had no standard therapeutic options. An expansion cohort at maximum tolerated dose (MTD) is planned. The starting dose of PQR309 was 10mg OD. The dose limiting toxicity (DLT) period was the first cycle of treatment, 21 days (d). Paired tumour biopsies (PTB) were collected. Results: 25 pts (18F:7M) were enrolled as of January 2015 and treated at 11 doses ranging from 10-150mg. Common adverse events (AE) ( ≥ 30% pts) included fatigue, hyperglycaemia, nausea, diarrhea, constipation, rash, anorexia and vomiting. Grade (G) 3/4 drug-related AE were seen in 11 and 3 pts respectively. The most common drug-related AE ≥ G3 was hyperglycaemia observed in 7 pts. DLT occurred in 2/6 pts at 100mg OD asso...