Adult patients with advanced solid tumours received peposertib 100-200 mg once daily or 150-400 mg twice daily (BID) in 21-day cycles.
Thirty-one patients were included (median age 66 years, 61% male). One dose-limiting toxicity, consisting of mainly gastrointestinal, non-serious adverse events (AEs) and long recovery duration, was reported at 300 mg BID. The most common peposertib-related AEs were nausea, vomiting, fatigue and pyrexia. The most common peposertib-related Grade 3 AEs were maculopapular rash and nausea. Peposertib was quickly absorbed systemically (median Tmax 1.1-2.5 h). The p-DNA-PK/t-DNA-PK ratio decreased consistently in peripheral blood mononuclear cells 3-6 h after doses ≥100 mg. The best overall response was stable disease (12 patients), lasting for ≥12 weeks in seven patients.
Peposertib was well-tolerated and demonstrated modest efficacy in unselected tumours. The MTD was not reached; the RP2D was declared as 400 mg BID. Further studies, mainly with peposertib/chemo-radiation, are ongoing.
NCT02316197.