Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC
Condition: Non Small Cell Lung Cancer
MeSH terms: Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of
      epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer
      (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase
      inhibitor (TKI) agent.

      Part A will assess the effect of osimertinib on the pharmacokinetic (PK) parameters of
      fexofenadine, following single and multiple oral dosing of osimertinib in a fasted state.

      Continuous Access will allow patients further access to osimertinib after the PK phase (Part
      A). All patients from Part A who completed treatment may continue to receive osimertinib 80
      mg once daily until: they are no longer deriving clinical benefit; or any other reason
    

Detailed description: 
      This is a Phase I, open-label, non-randomised, two-part study in patients with EGFRm+ NSCLC
      who have progressed on an EGFR-TKI.

      The PK phase will assess the effect of osimertinib on the PK parameters of fexofenadine
      following both single and multiple oral dosing of osimertinib. Continued access will provide
      patients with further access to osimertinib after the PK phase.

      The study will be conducted at approximately 10 sites across Asia and Western Europe, with
      approximately 24 patients enrolled in order to achieve at least 18 evaluable patients.
      Additional patients may be dosed to ensure the minimum number of evaluable patients.

      PK phase The PK phase is a non-randomised, open-label, 2-period design. Treatment Period 1
      and Treatment Period 2 are separated by a 3 to 7 day washout period between doses. A study
      flow chart for the PK phase is presented in Figure 1. Patients will receive osimertinib 80 mg
      as a single dose on Day 1 of Treatment Period 2, then 80 mg once daily for 38 days (from Day
      4 to Day 41 in Treatment Period 2). Patients will also receive a single oral dose of
      fexofenadine on Day 1 in Treatment Period 1, and on Days 1 and 39 in Treatment Period 2.

      Continued access On completion of the PK phase (ie, following collection of the 72-hour
      fexofenadine sample on Day 42), patients may continue to take osimertinib tablets (80 mg once
      daily) as a single agent in continued access if they and the Investigator agree that this is
      appropriate. This will continue until the Investigator believes they are no longer deriving
      clinical benefit, or they stop taking osimertinib for any other reason. No clinical data will
      be collected during this phase other than sudden death of unknown reason, serious adverse
      events (SAEs) that may be related to osimertinib, outcomes of pregnancy and drug
      dispensing/accountability.

      If a patient discontinues treatment during the PK phase, they will return to the clinic for
      follow-up assessments 30 days (±7 days) after their last dose of treatment in the PK phase.
      If the patient's last dose of osimertinib is in continued access, the patient should be
      contacted 30 days after their last dose of osimertinib to follow-up any existing SAEs,
      monitor for new SAEs that may be related to the IP, and record any sudden deaths of unknown
      cause.
    

Intervention name(s): Fexofenadine tablet dosing; Osimertininb tablet dosing
Intervention type(s): Drug; Drug
Intervention description(s): Fexofenadine (P-gp substrate) 120mg taken once daily on Days 1 in Treatment Period 1 and Day 1 and Day 39 in Treatment Period 2; Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2
Other intervention name(s): Mucinex, Allegra, Select, Rugby; TAGRISSO™
Intervention MeSH terms: Fexofenadine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: oncology; cancer; non small cell lung cancer; anticancer drug; lung neoplasms; pharmacokinetics; AZD9291; osimertinib; fexofenadine; TAGRISSO™; EGFR genes