Safety, tolerability, pharmacokinetics and pharmacodynamics of AZD8055 in advanced solid tumours and lymphoma

摘要: This study assessed the safety, tolerability, pharmacokinetics and pharmacodynamics of first-in-class dual mammalian target rapamycin complex (mTORC)1/mTORC2 inhibitor, AZD8055. Patients with advanced solid malignancies or lymphomas were recruited into this phase I, open-label, dose-escalation AZD8055 starting at 10 mg twice-daily oral dosing (BID). Forty-nine patients received Dose-limiting toxicities reported 40 mg (n=1), 90 mg (n=1) 120 mg (n=3) BID; all grade 3 rises in transaminases, reversible patients, apart from one who had liver metastases. The maximum tolerated dose was defined as BID. most frequent adverse events to be related increased alanine aminotransferase (22%), aspartate (22%) fatigue (16%). rapidly absorbed (median tmax ∼0.5 h) exposure increasing doses. Seven stable disease for ⩾4 months. Partial metabolic responses, by fluorodeoxyglucose positron emission tomography, observed ⩾40 mg BID (n=8 day 35). is Apart elevated which occurred levels, drug an acceptable toxicity profile; however, no RECIST responses seen.