TSR-011 320- and 480-mg Q24h doses exceeded the maximum tolerated dose. Secondary objectives included pharmacokinetics. The primary objective was to evaluate safety and tolerability. In this sequential, open-label, phase 1 trial (NCT02048488), patients received doses of 30 mg, escalated to 480 mg every 24 hours (Q24h), followed by an expansion cohort of patients with ALK-positive cancers. Here, we report the safety, tolerability and recommended phase 2 dose (RP2D) of TSR-011 in patients with relapsed or refractory ALK- and TRK-positive advanced cancers. TSR-011 is a dual ALK and tropomyosin-related kinase (TRK) inhibitor, active against ALK inhibitor resistant tumours in preclinical studies. Anaplastic lymphoma kinase ( ALK) gene rearrangements are oncogenic drivers in non-small-cell lung cancer (NSCLC).