Evaluation of Extended Dosing Interval of Osimertinib in EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The primary objective of this study is to evaluate the **non-inferiority** of an extended dosing interval of osimertinib compared to the standard dosage in patients with EGFR mutated locally advanced or metastatic non-small cell lung cancer. This is clinically relevant as it may offer a more convenient dosing schedule without compromising efficacy, potentially improving patient adherence and quality of life.

Secondary objectives include:

• Assessing the efficacy of osimertinib 80 mg every other day (QOD) compared with osimertinib 80 mg once daily (QD).
• Evaluating the safety profile of osimertinib 80 mg QOD compared with osimertinib 80 mg QD.
• Assessing disease-related symptoms and health-related quality of life in patients treated with osimertinib 80 mg QOD compared to osimertinib 80 mg QD.
• Evaluating the cost-effectiveness for patients treated with osimertinib 80 mg QOD compared with osimertinib 80 mg QD.
• Assessing the effect of osimertinib 80 mg QOD compared with osimertinib 80 mg QD on the risk of developing central nervous system metastases over time.
• Evaluating the feasibility and patient adherence to osimertinib 80 mg QOD compared with osimertinib 80 mg QD.

The clinical trial involves participants diagnosed with **EGFR mutated locally advanced or metastatic non-small cell lung cancer**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a sufficient understanding of the local language to complete questionnaires and must be able to provide informed consent. The trial does not include vulnerable populations. Participants have been previously treated with first-line osimertinib, with or without chemotherapy, for a minimum of three months, and have shown a response on radiologic assessment. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the **non-inferiority** of an extended dosing interval of **osimertinib** compared to the standard dosage in patients with **EGFR mutated locally advanced or metastatic non-small cell lung cancer**. This trial is a randomized, double-blind, controlled study, categorized as a low-intervention clinical trial, as all investigational medicinal products are authorized and used within the terms of their marketing authorization. The trial is expected to commence recruitment on May 1, 2025, and conclude by May 1, 2031, with a maximum treatment period of 104 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), ability to provide informed consent, and a confirmed diagnosis of locally advanced or metastatic NSCLC with specific **EGFR** mutations. Following the screening, participants will be randomized to receive either the standard or extended dosing regimen of osimertinib. Regular follow-up visits will be scheduled to monitor progression-free survival (PFS), overall survival (OS), patient-reported toxicity, quality of life, and other secondary endpoints. The end-of-study visit will assess the cumulative incidence of central nervous system (CNS) metastases and medication adherence.

The expected length of participant involvement is up to 104 weeks, contingent upon individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, withdrawal of consent, or any other medical condition that, in the opinion of the investigator, warrants discontinuation. The trial aims to provide valuable insights into the feasibility and potential benefits of an extended dosing interval of osimertinib, contributing to optimized treatment strategies for this patient population.

The clinical trial involves the administration of **osimertinib**, marketed under the name TAGRISSO, which is provided in the form of **film-coated tablets**. Each tablet contains 80 mg of the active substance **osimertinib**, a chemical compound also known by the synonym AZD9291. The tablets are intended for **oral** administration. The standard dosage regimen involves a maximum daily dose of 80 mg, with the treatment period extending up to 104 weeks. The primary objective of the trial is to evaluate the non-inferiority of an extended dosing interval of osimertinib compared to the standard dosage in patients with EGFR mutated locally advanced or metastatic non-small cell lung cancer.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The trial focuses solely on the administration of osimertinib. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the prescribed regimen. The pharmaceutical form and administration route are designed to optimize the bioavailability and therapeutic efficacy of the active substance.

The clinical trial aims to assess the efficacy of an extended dosing interval of **osimertinib** in patients with EGFR mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). The primary endpoint for evaluating efficacy is **progression-free survival (PFS)**. Secondary endpoints include overall survival (OS), patient-reported toxicity of any grade (excluding laboratory abnormalities), economic assessment, quality of life, cumulative incidence of central nervous system (CNS) metastases, and feasibility/medication adherence.

Measurements for these endpoints will be collected at specified intervals throughout the trial duration, which is estimated to conclude by May 2031. The trial is designed as a low-intervention study, utilizing authorized medicinal products within their marketing authorization terms. The trial will employ validated scales and patient-reported outcomes to gather data on quality of life and toxicity, while progression-free survival and overall survival will be assessed through radiologic evaluations and clinical follow-ups. The trial's main objective is to determine the non-inferiority of the extended dosing interval compared to the standard dosage of osimertinib.