AZD9291 US Expanded Access Program

A Multi-center, AZD9291 Expanded Access Program for the Treatment of Patients With Advanced/Metastatic EGFR T790M Mutation-positive Non-small Cell Lung Cancer (NSCLC) Who Have Received Prior EGFR TKI Therapy

To provide access to AZD9291 for adult patients with advanced/metastatic, epidermal growth factor receptor T790M mutation-positive non-small cell lung cancer.

- This is a multi-center, AZD9291 expanded access protocol for the treatment of adult patients with advanced/metastatic EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) who have received prior EGFR TKI therapy and at least one additional line of therapy (≥ 3rd line). Local testing is accepted for confirmation of T790 mutation status. Eligible patients will be enrolled to receive AZD9291 (80mg orally, once daily) for as long as the access program remains open and they are continuing to show clinical benefit, as judged by the treating physician

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any treatment protocol-specific procedures
• Patients aged at least 18 years
• Locally advanced or metastatic EGFRm NSCLC, not amenable to curative surgery or radiotherapy with confirmation of the presence of the T790M mutation
• Two lines of prior therapy including at least one EGFR TKI
• World Health Organization (WHO) performance status 0-2.
• Females of child-bearing potential must use adequate contraceptive measures, not be breast-feeding and have negative pregnancy test prior to start of dosing.
• Males patients should be willing to use barrier contraception.

Exclusion Criteria:

• Previous treatment with AZD9291

• Patients currently receiving (or unable to stop use at least 1 week prior to receiving the first dose of AZD9291) any treatment known to be potent inhibitors or inducers of CYP3A4

• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, active bleeding diatheses, or significantly impaired bone marrow reserve or organ function, including hepatic and renal impairment, which in the clinician's opinion would significantly alter the risk/benefit balance, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV).

• Patients with symptomatic CNS metastases who are neurologically unstable

• Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD

• Any of the following cardiac criteria:

  1. Mean resting corrected QT interval (QTc using Fredericia's formula) > 470 msec
  2. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block)
  3. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval

• Any unresolved toxicity from prior therapy Common Terminology Criteria for Adverse Events (CTCAE) > grade 3 at the time of starting treatment in the access program

• History of hypersensitivity to AZD9291 (or drugs with a similar chemical structure or class to AZD9291) or any excipients of these agents

• Males and females of reproductive potential who are not using an effective method of birth control and females who are pregnant or breastfeeding or have a positive (urine or serum) pregnancy test prior to access program entry