AZD6244 in Combination With Docetaxel Versus Docetaxel Alone in KRAS Mutation Positive NSCLC Patients

The primary objective of this study was to assess the efficacy in terms of overall survival (OS) of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC. Amendment 4 of the CSP altered the primary objective and outcome variable from progression-free survival (PFS) to OS, and the secondary outcome variable changed from OS to PFS.

The secondary objectives of the study were:

To further assess the efficacy of AZD6244 in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive locally advanced or metastatic NSCLC
To assess the safety and tolerability profile of AZD6244 in combination with docetaxel
To investigate the use of plasma and serum as a potential source of circulating free tumour DNA (cfDNA) for the analysis of KRAS mutation status
To investigate the PK of AZD6244 and N-desmethyl AZD6244 and any other known metabolites when AZD6244 is administered in combination with docetaxel.

The exploratory objectives of the study were:

To assess the prevalence, severity and change over time of advanced NSCLC cancer specific symptoms in patients receiving AZD6244 in combination with docetaxel and docetaxel alone
To explore potential biomarkers in residual tumour, plasma and/or serum taken for KRAS mutational analysis which may influence development of NSCLC (and associated clinical characteristics) and/or response (optional)
To investigate the relationship between AZD6244 and/or N-desmethyl AZD6244 and any other known metabolite plasma concentrations or exposure and clinical outcomes, efficacy, AEs, and/or safety parameters if deemed appropriate
To collect and store deoxyribonucleic acid (DNA), derived from a blood sample, for future exploratory research into genes that may influence response, eg, distribution, safety, tolerability, and efficacy of AZD6244 and/or agents used in combination and/or as comparators (optional).