Phase 3 Randomized Study of Pembrolizumab and Sacituzumab Govitecan Combination Versus Pembrolizumab Monotherapy in PD-L1 TPS ≥50% Metastatic NSCLC

The primary objective of this clinical study is to compare **pembrolizumab** in combination with **sacituzumab govitecan** versus pembrolizumab monotherapy in terms of **progression-free survival** and **overall survival** in patients with **metastatic non-small cell lung cancer** (NSCLC) with a PD-L1 TPS of 50% or greater. This is clinically relevant as it aims to determine the efficacy of the combination therapy in extending survival and delaying disease progression compared to standard monotherapy, potentially offering a more effective first-line treatment option for this patient population.

Secondary objectives include: - Comparing the combination therapy with pembrolizumab alone regarding the **objective response rate** per RECIST 1.1, as assessed by blinded independent central review. - Evaluating the **duration of response** per RECIST 1.1 for both treatment regimens. - Assessing the mean change from baseline in **global health status/quality of life**, physical functioning, role functioning, dyspnea, cough, and chest pain. - Evaluating the **time to deterioration** in these health-related quality of life measures. - Assessing the **safety and tolerability** of the combination therapy compared to pembrolizumab monotherapy.

The clinical trial involves a total of **461 participants** diagnosed with **metastatic non-small cell lung cancer**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer, and confirmation that therapies targeting EGFR, ALK-1, or ROS-1 are not indicated as primary treatment. Additionally, participants must have provided tumor tissue demonstrating a PD-L1 tumor proportion score of at least 50% as assessed by immunohistochemistry. The trial includes individuals with a life expectancy of at least three months. The study population is characterized by a diverse range of health statuses, and both genders are represented. The trial also considers vulnerable populations, although specific lifestyle factors such as diet or physical activity are not detailed in the available data.

The clinical trial is a **Phase 3**, randomized, active-comparator-controlled study designed to evaluate the efficacy and safety of **pembrolizumab** in combination with **sacituzumab govitecan** versus pembrolizumab monotherapy as a first-line treatment for participants with **metastatic non-small cell lung cancer** (NSCLC) exhibiting a PD-L1 tumor proportion score (TPS) of 50% or greater. The trial employs a double-blind methodology to ensure unbiased results, with participants randomly assigned to either the combination therapy group or the monotherapy group. The study is expected to span approximately five years, with an estimated end date in September 2028.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histologically or cytologically confirmed diagnosis of metastatic NSCLC and a life expectancy of at least three months. Following randomization, participants will attend regular follow-up visits to monitor progression-free survival (PFS) and overall survival (OS), which are the primary endpoints of the study. Secondary endpoints include objective response, duration of response, and changes in quality of life as measured by the EORTC QLQ-C30 and QLQ-LC13 questionnaires. The end-of-study visit will conclude the participant's involvement, assessing final outcomes and any adverse events experienced during the trial.

The expected length of participant involvement is up to 24 months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent by the participant. The trial aims to provide comprehensive data on the comparative effectiveness of the combination therapy versus monotherapy, contributing valuable insights into treatment strategies for metastatic NSCLC.

The clinical trial involves the administration of two **experimental medications**: **Sacituzumab Govitecan** and **Pembrolizumab**. **Sacituzumab Govitecan** is classified under the ATC code L01FX17 and is administered as a **biologic**. It is provided in a pharmaceutical form identified as PHF00230MIG, specifically for **intravenous infusion**. The dosing regimen for Sacituzumab Govitecan is set at a maximum daily dose of 10 mg/kg, with a total maximum dose of 700 mg/kg over a treatment period of up to 24 weeks. The administration schedule and participant compliance are monitored to ensure adherence to the protocol.

**Pembrolizumab**, marketed under the name **Keytruda**, is a **biological** product with the ATC code L01FF02. It is supplied as a 25 mg/mL concentrate for solution for infusion, intended for **intravenous infusion**. The maximum daily dose for Pembrolizumab is 200 mg, with a total maximum dose of 7000 mg over a 24-week treatment period. Pembrolizumab is also known by its sponsor product code MK-3475 and is produced by Merck Sharp & Dohme B.V. The trial compares the efficacy of Pembrolizumab in combination with Sacituzumab Govitecan versus Pembrolizumab monotherapy in participants with metastatic non-small cell lung cancer, with a focus on progression-free survival and overall survival.

Efficacy in this clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints include **Progression-Free Survival (PFS)** and **Overall Survival (OS)**. These endpoints will be evaluated to compare the efficacy of pembrolizumab in combination with sacituzumab govitecan versus pembrolizumab monotherapy in participants with metastatic non-small cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) of 50% or greater.

Secondary endpoints will include Objective Response (OR), Duration of Response (DOR), and various patient-reported outcomes measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and the Lung Cancer 13 (EORTC QLQ-LC13). These include changes from baseline in global health status, physical functioning, role functioning, dyspnea, cough, and chest pain scores, as well as time to deterioration (TTD) in these domains. Additionally, the number of participants experiencing adverse events (AEs) and those discontinuing treatment due to AEs will be recorded.

The efficacy parameters will be assessed at specified timepoints throughout the trial, with progression-free survival and overall survival being evaluated by a blinded independent central review according to RECIST 1.1 criteria. Patient-reported outcomes will be collected using validated questionnaires, ensuring a comprehensive evaluation of both clinical and quality of life aspects of the treatment.