Efficacy of PD-L1 and TIGIT Targeting in TLS-Positive Advanced or Metastatic NSCLC in Systemically Naïve or Chemotherapy and PD1/PDL1 Antagonist-Treated Adults

The primary objective of this study is to evaluate the **efficacy** of a treatment regimen targeting **PD-L1** and **TIGIT** in tumors characterized by the presence of tertiary lymphoid structures (TLS) in adult patients with advanced or metastatic non-small cell lung cancer (NSCLC). This is clinically relevant as it aims to improve therapeutic outcomes in a specific subset of NSCLC patients who have not previously been treated with CD137 agonists or investigational immune checkpoint blockade therapies, including anti-TIGIT and anti-LAG3. The study focuses on patients who are either treatment-naïve or have been previously treated with chemotherapy and PD1/PDL1 antagonists, ensuring they have adequate organ function and a performance status of WHO 0-1 or ECOG 0-1. Patients with active or a history of autoimmune disease or immune deficiency, as well as pregnant or breastfeeding women, are excluded from the study.

The clinical trial involves **adult patients** with histologically confirmed TLS-positive advanced or metastatic **non-small cell lung cancer (NSCLC)**. Participants are either naïve to systemic treatment or have been previously treated with chemotherapy and PD1/PDL1 antagonists, but not with CD137 agonists or investigational immune checkpoint blockade therapies, such as anti-TIGIT or anti-LAG3. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically includes adults and older adults. Participants must have adequate organ function and a performance status of WHO 0-1 or ECOG 0-1. Individuals with active or a history of autoimmune disease or immune deficiency are excluded, as well as pregnant or breastfeeding women. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations.

The clinical trial is designed to evaluate the efficacy of a treatment targeting **PD-L1** and **TIGIT** in tumors with tertiary lymphoid structures in adult patients with advanced or metastatic non-small cell lung cancer (NSCLC). This study is a Phase 4, randomized, double-blind, controlled trial. The estimated recruitment start date is May 2, 2024, with an anticipated end date of May 31, 2029. Participants will be involved in the study for the duration of the trial unless early termination criteria are met, such as adverse events or withdrawal of consent.

The trial will commence with an inclusion (screening) visit to assess eligibility based on specific criteria, including histologically confirmed TLS-positive NSCLC, adequate organ function, and performance status (WHO 0-1; ECOG 0-1). Patients with a history of autoimmune disease or immune deficiency, as well as pregnant or breastfeeding women, will be excluded. Following successful screening, participants will be randomized to receive either the investigational treatment or a control. Study visits will be scheduled at regular intervals to monitor treatment efficacy and safety, with follow-up visits to assess ongoing health status and any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary and secondary endpoints.

Participants are expected to adhere to the study protocol throughout the trial duration. Conditions that may lead to early termination from the study include significant protocol deviations, adverse reactions, or voluntary withdrawal. The trial aims to provide comprehensive data on the treatment's efficacy and safety profile, contributing to the understanding of therapeutic strategies for NSCLC with tertiary lymphoid structures.

The clinical trial involves the administration of an **experimental medication**. However, specific details regarding the name, pharmaceutical form, dosage, route, and frequency of administration of the experimental medication are not provided in the available data. The trial documentation does not specify whether the medication is a **paediatric formulation** or if it has an **orphan drug** designation. Additionally, there is no information on the maximum daily dose, total dose, or treatment period for the experimental medication.

In this study, there is no mention of any **non-experimental treatments** such as standard-of-care therapy, placebo, or comparator treatment being used. The data does not provide details on any additional relevant information about drug administration, dosing schedules, or participant compliance monitoring. Consequently, the trial documentation lacks comprehensive information on the treatment protocols and participant management strategies.

The clinical trial is designed to assess efficacy within the context of a Phase 4 study. The trial is scheduled to commence recruitment on May 2, 2024, with an estimated completion date of May 31, 2029. The efficacy assessment will be conducted using parameters that are standard for Phase 4 trials, although specific endpoints and methods for measuring efficacy are not detailed in the provided data. The trial will adhere to rigorous scientific and methodological standards typical of post-marketing surveillance studies, ensuring that the efficacy data collected is robust and reliable. The analysis will likely involve statistical methods appropriate for evaluating treatment effects in a real-world setting, consistent with the objectives of a Phase 4 trial.