A Phase III, Open Label, Randomized Study of Osimertinib versus Platinum-Based Doublet
Chemotherapy for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer
whose Disease has Progressed with Previous Epidermal Growth Factor Receptor Tyrosine
Kinase Inhibitor Therapy and whose Tumours harbour a T790M mutation within the Epidermal
Growth Factor Receptor Gene
Additional locations may be listed on ClinicalTrials.gov for NCT02151981.
See trial information on ClinicalTrials.gov for a list of participating sites.
This is a phase III, open label, randomized study assessing Osimertinib (80 mg, orally,
once daily) versus platinum-based doublet chemotherapy (standard of care) in subjects
with confirmed diagnosis of Epidermal Growth Factor Receptor (EGFR) mutation positive
NSCLC, who have progressed following prior therapy with an approved Epidermal Growth
Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) agent and whose tumours harbour a
T790M mutation within the EGFR Gene. Subjects must be chemotherapy naive and must agree
to provide a biopsy for central confirmation of T790 mutation status following confirmed
disease progression on their first line EGFR-TKI treatment (e.g. erlotinib, gefitinib or
afatinib). Suitable subjects will then be randomized to receive either Osimertinib (80mg
orally, once daily) or platinum-based doublet chemotherapy (pemetrexed 500 mg/m2 +
carboplatin area under the plasma concentration-time curve AUC 5 or pemetrexed 500 mg/m2
+ cisplatin 75 mg/m2) on Day 1 of every 21-day cycle in a 2:1 (Osimertinib:
platinum-based doublet chemotherapy) ratio. Once subjects on the platinum-based doublet
chemotherapy arm are determined to have objective radiological progression according to
RECIST 1.1 by the investigator and confirmed by independent central imaging review, they
will be given the opportunity to begin treatment with Osimertinib 80mg, once daily. These
subjects may continue treatment with Osimertinib even after disease progression, as long
as they are continuing to show clinical benefit, as judged by the investigator. The
primary objective of the study is to assess the efficacy of Osimertinib compared with
platinum-based doublet chemotherapy by assessment of Progression Free Survival (PFS),
using investigator assessments according to Response Evaluation Criteria in Solid Tumours
(RECIST 1.1), as well as asensitivity analysis of Progression Free Survival using Blinded
Independent Central Review (BICR).
Lead OrganizationAstraZeneca Pharmaceuticals LP
