Safety, Tolerability & Potential Anti-cancer Activity of Increasing Doses of AZD5363 in Different Treatment Schedules

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics
and Preliminary Anti-tumour Activity of Ascending Doses of AZD5363 under Adaptable Dosing
Schedules in Patients with Advanced Solid Malignancies.

Inclusion Criteria:

- Aged at least 18 years.

- Parts A,B: The presence of a solid, malignant tumour, excluding lymphoma, that is
resistance to standard therapies or for which no standard therapies exist.

- ER+/HER2+ breast, ovarian, cervical, endometrial cancer, or other solid cancers,
resistance to standard therapies with a PIK3CA gene mutation (Part C), AKT1 gene
mutation (Part D) or a dysregulatory aberration on the PIK/AKT pathway (Part D),
advanced or metastatic ER+ positive breast cancer that has an AKT1 gene mutation (Part
E) or advanced or metastatic ER+ positive breast cancer that has a PTEN gene mutation
(Part F).

- The presence of at least one lesion that can be accurately assessed at baseline by CT,
MRI or plain X-ray and is suitable for repeated assessment. Estimated life expectancy
of more than 12 weeks.

- Estimated life expectancy of more than 12 weeks.

Exclusion Criteria:

- Clinically significant abnormalities of glucose metabolism.

- Spinal cord compression or brain metastases unless asymptomatic, treated and stable
(not requiring steroids).

- Evidence of severe or uncontrolled systemic diseases, including active bleeding
diatheses or active infections including hepatitis B, C and HIV.

- Evidence of clinically significant cardiac abnormalities, uncontrolled hypotension,
left ventricular ejection fraction below the lower limit of normal for the site or
experience of significant cardiac interventional procedures.

- A bad reaction to AZD5363 or any drugs similar to it in structure or class.