Common use of Exploratory Objectives Clause in Contracts

Exploratory Objectives. To investigate the relationship between plasma AZD5363 exposure and plasma concentration of exploratory biomarkers and efficacy. Biomarkers may include, but are not restricted to, somatic mutation or amplification of genes on the PI3 Kinase and related pathways in circulating tumour plasma DNA (ctDNA). • To obtain a preliminary assessment of AZD5363 treatment effect by quantitative change in circulating tumour cells (CTCs). • To investigate the concordance of PIK3CA mutation status between per-patient analyses of blood and archival tumour tissue samples. • To explore changes in WHO performance status in patients treated with AZD5363 in combination with weekly paclitaxel compared with weekly paclitaxel plus placebo. • To collect optional matched pre-and post- treatment tumour biopsy samples to conduct assessment of the PDc effect of therapy compared to baseline. • To collect and store archival tumour samples and analyse surplus blood or tissue, for potential future exploratory research into factors that may influence development of cancer and/or response to AZD5363 (where response is defined broadly to include efficacy, tolerability or safety). Biomarkers may include, but are not restricted to, somatic mutation or amplification of genes on the PI3 kinase and related pathways, PTEN protein expression and AKT protein expression. This exploratory analysis will be reported separately. • To obtain blood samples for DNA extraction for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to AZD5363 treatment and/or susceptibility to cancer. This exploratory analysis will be reported separately.

Exploratory Objectives. The exploratory objective of the First part (Part A) of this study is • To investigate the relationship between plasma AZD5363 exposure and plasma concentration concentrations of exploratory biomarkers and efficacy. Biomarkers may include, but are not restricted to, somatic mutation or amplification of genes on the PI3 Kinase kinase and related pathways in circulating tumour plasma DNA (ctDNA)cfDNA. • To obtain a preliminary p reliminary assessment of AZD5363 treatment effect by quantitative change in circulating tumour cells (CTCs). • To investigate the concordance of PIK3CA mutation status between per-patient analyses of blood and archival tumour tissue samples. • To explore changes in WHO performance status in patients treated with AZD5363 in combination with weekly paclitaxel compared with weekly paclitaxel plus placebo. • To collect optional matched pre-and post- treatment tumour biopsy samples to conduct assessment of the PDc PD effect of therapy compared to baseline. • To collect and store archival tumour samples and analyse surplus blood or tissue, for potential future exploratory research into factors that may influence development of cancer and/or response to AZD5363 (where response is defined broadly to include efficacy, tolerability or safety). Biomarkers may include, but are not restricted to, somatic mutation or amplification of genes on the PI3 kinase and related pathways, PTEN protein expression and AKT protein expression. This exploratory analysis will be reported separately. • To obtain blood samples for DNA deoxyribonucleic acid (DNA) extraction for future exploratory research into genes/genetic variation that may influence response (iei.e., distribution, safety, tolerability and efficacy) to AZD5363 treatment and/or susceptibility to cancer. This exploratory analysis will be reported separately.