A Phase 1, open-label, multicentre study to compare the capsule and tablet formulations of AZD5363 and explore the effect of food on the pharmacokinetic exposure, safety and tolerability of AZD5363 in patients with advanced solid malignancies: OAK

**Purpose:** AZD5363 is a powerful pan-AKT inhibitor initially developed as a capsule. To enhance patient convenience and streamline manufacturing, a tablet form was created. This study aimed to evaluate the pharmacokinetic (PK) comparability of both formulations (Part A) and to examine the impact of food (Part B) on the PK and safety of the tablet.

**Methods:** Adults with advanced solid tumors were administered AZD5363 at a dose of 480 mg twice daily (bid) in a partially fasted state, first by tablet (Week 1) and then by capsule (Week 2), following a ’4-days-on/3-days-off’ schedule (Part A). PK parameters were analyzed using predefined 90% confidence intervals (CIs) for AUCτ and Cmax ratios, with a target range of 0.75-1.33 to determine comparability. In Part B, a new group of patients received the AZD5363 tablet under the same conditions as Part A, except that on PK assessment days, the tablet was taken after an overnight fast (Week 1) and after a standard meal (Week 2).

**Results:** Among the evaluable patients (N = 11), the geometric least-squares mean ratios (tablet:capsule) for AUCτ and Cmax were 0.90 (0.77-1.06) and 1.02 (0.86-1.20), respectively, indicating comparable PK profiles in the partially fasted state. The safety data for the tablet and capsule were also similar. The PK profiles of the tablet showed a later tmax and lower Cmax after food compared to overnight fasting. The fed versus fasted AUCτ and Cmax ratios were 0.89 (0.76-1.05) and 0.67 (0.55-0.82), respectively (N = 9). The safety and tolerability of the tablet were consistent between the fed and fasted conditions.

**Conclusions:** The PK and safety/tolerability profiles of AZD5363 were comparable between the tablet and capsule formulations. While food did not affect the overall bioavailability of AZD5363, it did reduce the absorption rate, without any significant impact on safety or tolerability.