Background: Loss of PTEN function leads to increased PI3Kβ signalling. AZD8186 (AZD) exhibits significant anti-tumour activity in PTEN-deficient preclinical models, particularly when combined with anti-androgens or the dual mTORC1/2 inhibitor vistusertib (AZD2014). Here we report on the dose-finding part of this Phase 1 study. Methods: AZD single agent was administered twice daily (BD) in 3 different schedules (5 days on/ 2 days off, 2 days on/ 5 days off and continuous). Escalating doses of AZD were evaluated in cohorts of 3-6 patients treated until progression, unacceptable toxicity, or consent withdrawal. Accrual is ongoing in the combination arms with vistusertib or abiraterone acetate. Results: As of 16 Jan 2017, 87 patients have received AZD at doses of 30–360 mg BD, with 28 confirmed as PTEN deficient (IHC). The selected RP2D for the 5 days on/2 days off monotherapy schedule is 60 mg BD. PK parameters show that systemic exposures to AZD and its major active metabolite increase in a dose proportional manner. 69 serious adverse events (SAEs) were reported in 31 patients on AZD monotherapy with 23 SAEs considered possibly related to AZD. In the 5/2 schedule: 5 dose limiting toxicities (G3 rash with ≥G2 fever and/or chills) were observed in 5 patients at doses of 120-360mg. Adverse events ≥G1 in > 20% included diarrhoea, nausea, fatigue, LFT elevations and decreased appetite. 20 patients remained on study for > 100 days. Dose-dependent target inhibition has been demonstrated in surrogate tissue (platelets). Evaluation of direct tumour target engagement in paired biopsies is currently ongoing. Preliminary efficacy: Confirmed PRs seen in a CRPC patient (BRCA2 and androgen receptor mutant) treated in combination with vistusertib (on study for 411 days) and in one ongoing monotherapy PTEN-deficient colorectal cancer patient (on study > 329 days). Updated data will be presented. Conclusions: AZD has potential for treatment of PTEN-deficient tumours. Investigation of the safety/tolerability and preliminary efficacy in combination with vistusertib or abiraterone acetate is continuing. Clinical trial information: NCT01884285