Neoplasms

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Carcinoma, Non-Small-Cell Lung

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Antineoplastic Agents

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Osimertinib

Fexofenadine

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polysaccharide-K

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Sequential treatments of fexofenadine alone followed by osimertinib + fexofenadine, followed by osimertinib alone, followed by osimertinib + fexofenadine

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

Fexofenadine tablet dosing

Osimertininb 80 mg taken once daily on Day 1 and Days 4 to 41 in Treatment Period 2

Osimertininb tablet dosing

Emiliano C Aller, M.D., Ph.D.

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

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.

Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC

An Open-label, Non-randomised, Phase I Study to Assess the Effect of Single and Multiple Oral Doses of Osimertinib (TAGRISSO™) on the Pharmacokinetics of a P-glycoprotein Probe Drug (Fexofenadine) in Patients With Advanced EGFRm NSCLC That Have Progressed on a Prior EGFR-TKI Regimen

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

To characterize the pharmacokinetics of fexofenadine by assessment of maximum plasma fexofenadine concentration.

To characterize the pharmacokinetics of fexofenadine by assessment of area under the plasma concentration time curve from zero to infinity

To characterize the pharmacokinetics of fexofenadine by assessment of time to reach maximum plasma concentration

To characterize the pharmacokinetics of fexofenadine by assessment of area under plasma concentration-time curve from time zero to the last quantifiable time point

To characterize the pharmacokinetics of fexofenadine by assessment of apparent plasma clearance following oral administration

To characterize the pharmacokinetics of fexofenadine by assessment of apparent volume of distribution

To characterize the pharmacokinetics of fexofenadine by assessment of terminal rate constant

To characterize the pharmacokinetics of fexofenadine by assessment of terminal half-life

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of trough concentrations

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of area under plasma concentration-time curve from time zero to 72 hours post-dose

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of maximum plasma drug concentration

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of Time to reach maximum plasma concentration

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) maximum plasma drug concentration

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of area under plasma concentration time curve during the dosing interval

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of maximum plasma concentration at steady state

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of minimum plasma concentration at steady state

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of apparent plasma clearance following oral administration at steady state

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) area under plasma concentration time curve during the dosing interval

To characterize the pharmacokinetics of osimertinib and metabolites (AZ5104 and AZ7550) by assessment of metabolite to parent ratio (AZ5104:osimertinib, AZ7550:osimertinib) maximum plasma concentration at steady state

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC	NCT02908750	Non Small Cell ...	Fexofenadine ta... Osimertininb ta...	18 Years - 130 Years	AstraZeneca
Study to Assess the Effect of Osimertinib (TAGRISSO™ ) on Blood Levels of Fexofenadine in Patients With EGFRm+ NSCLC	NCT02908750	Non Small Cell ...	Fexofenadine ta... Osimertininb ta...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for osimertininb tablet dosing