A phase 1 study of the PI3K/mTOR inhibitor PQR309 evaluating safety, pharmacokinetics (PK) and pharmacodynamics (PD) in patients (pts) with advanced solid tumors.

Abstract

2560Background: PQR is an oral pan-PI3K, mTORC1/mTORC2 inhibitor in clinical development. Methods: A Phase I trial of PQR to evaluate safety, PK and PD in pts with advanced solid tumors was performed, using the standard “3+3” design. Pts with ECOG PS of 0-1 were treated with escalating doses of PQR administered on a once daily continuous dosing schedule (qd). The dose limiting toxicity (DLT) period was the first 21 days of treatment. PK samples were obtained at predefined time points. Blood samples for the evaluation of glucose, insulin and c-peptide as PD markers were obtained at multiple time points. Results: 16 pts (11F:5M) were enrolled as of November 30 2015 and treated at 3 doses of PQR (80, 100 and 120 mg) qd. Median duration of therapy was 50 days (range 7 – 255). Adverse events (AEs) in ≥ 50% pts included fatigue, hyperglycemia, rash, nausea, vomiting, diarrhea and weight loss. Drug related grade 3 AEs seen in more than 1 pt were fatigue, hyperglycemia, rash and elevated transaminases. DLT’s were...