AZD9291 Versus Platinum-Based Doublet-Chemotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This is a phase III, open label, randomized study assessing AZD9291 (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 AZD9291 (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 (AZD9291: 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 AZD9291 80mg, once daily. These subjects may continue treatment with AZD9291 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 AZD9291
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).

Inclusion Criteria:

- Subjects with histologically or cytologically documented NSCLC.

- Locally advanced or metastatic NSCLC

- Radiological documentation of disease progression following 1st line EGFR TKI
Treatment without any further treatment

- Eligible to receive treatment with the selected doublet-chemotherapy

- Central confirmation of T790M+ mutation status

- World Health Organization (WHO) performance status 0-1

- At least one lesion, not previously irradiated.

Exclusion Criteria:

- • Prior neo-adjuvant or adjuvant chemotherapy treatment within 6 months prior of
starting 1st EGFR TKI treatment

- Treatment with more than one prior line of treatment for advanced NSCLC

- Treatment with an approved EGFR-TKI (e.g.,erlotinib, gefitinib, afatinib) within 8
days or approximately 5x half-life of the first dose of study treatment

- Any investigational agents or other anticancer drugs from a previous treatment regimen
or clinical study within 14 days of the first dose of study treatment

- Previous treatment with AZD9291, or a 3rd generation EGFR TKI

For subjects who cross-over to AZD9291:

- 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.

- At least 14 days since last dose of platinum-based doublet chemotherapy