A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Treatment With a Platinum Doublet Chemotherapy and Immunotherapy

The primary objective of this study is to compare **Progression-Free Survival (PFS)** in participants with metastatic non-small cell lung cancer treated with MK-7684A plus docetaxel versus normal saline placebo plus docetaxel, as well as MK-7684A alone versus normal saline placebo plus docetaxel. This comparison is conducted using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and assessed by Blinded Independent Central Review (BICR). Evaluating PFS is clinically relevant as it provides insights into the efficacy of the treatment regimens in delaying disease progression, which is crucial for improving patient outcomes in this population.

Secondary objectives include:

• Evaluating the **Objective Response Rate (ORR)** in participants treated with MK-7684A plus docetaxel, MK-7684A alone, or normal saline placebo plus docetaxel, according to RECIST 1.1 by BICR.
• Assessing **Overall Survival (OS)** in the same participant groups, which is a critical endpoint for determining the long-term benefits of the treatments.
• Determining the **Duration of Response (DOR)** per RECIST 1.1 as assessed by BICR, which helps in understanding the sustainability of the treatment response.
• Evaluating the **safety and tolerability** of the treatment regimens, which is essential for assessing the risk-benefit profile of the interventions.

The clinical trial involves a total of **105 participants** diagnosed with **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 confirmed diagnosis of metastatic non-small cell lung cancer, adequate organ function, and a life expectancy of at least three months. The trial includes individuals who have experienced disease progression following prior treatments, such as anti-PD-1/PD-L1 monoclonal antibodies and platinum doublet chemotherapy. Both genders are represented, and the trial includes a vulnerable population. Participants are required to have measurable disease and provide tumor tissue for PD-L1 biomarker analysis. Lifestyle considerations such as diet and physical activity are not specified, but participants must adhere to contraceptive guidelines if applicable. The trial aims to evaluate the efficacy of MK-7684A in combination with docetaxel compared to a placebo with docetaxel, focusing on progression-free survival as per RECIST 1.1 criteria.

The clinical trial is a **randomized**, **double-blind**, controlled study designed to evaluate the efficacy and safety of MK-7684A, a combination of **pembrolizumab** and **vibostolimab**, with or without **docetaxel**, compared to docetaxel monotherapy in participants with metastatic **non-small cell lung cancer** (NSCLC) who have experienced disease progression following treatment with a platinum doublet chemotherapy and immunotherapy. The trial is expected to span approximately six years, with an estimated recruitment start date of April 15, 2021, and an anticipated end date of August 13, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a confirmed diagnosis of metastatic NSCLC, adequate organ function, and measurable disease as per RECIST 1.1 criteria. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety, with assessments conducted by a Blinded Independent Central Review (BICR). The primary endpoint is progression-free survival (PFS), while secondary endpoints include objective response, overall survival, duration of response, and the incidence of adverse events.

The expected duration of participant involvement is up to 156 weeks, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or determination by the investigator that continued participation is not in the participant's best interest. The trial aims to provide valuable insights into the potential benefits of MK-7684A in combination with docetaxel for patients with advanced NSCLC.

The clinical trial involves the administration of **MK-7684A**, an experimental medication formulated as a **solution for infusion**. This investigational product contains two active substances: **pembrolizumab** and **vibostolimab**, both of which are proteins of non-chemical origin. The medication is administered via **intravenous infusion**. The maximum daily dose is 400 mg, with a total maximum dose of 20,800 mg over a treatment period of 156 days. The administration schedule and participant compliance are monitored throughout the trial to ensure adherence to the dosing regimen.

A **placebo** is used in the study as a comparator to MK-7684A. The placebo is a normal saline solution, serving as a control to evaluate the efficacy and safety of the experimental treatment. The placebo is administered in the same manner as MK-7684A, ensuring blinding and consistency in the trial design.

**Docetaxel** is also utilized in the trial as a standard-of-care therapy. It is provided as a **concentrate for solution for infusion** and is administered via **intravenous infusion**. The maximum daily dose of docetaxel is 75 mg/m², with a total maximum dose of 3,900 mg/m² over the same treatment period of 156 days. The administration of docetaxel follows established protocols for its use in treating metastatic non-small cell lung cancer, and participant compliance is closely monitored to ensure accurate assessment of treatment outcomes.

The efficacy of the clinical trial will be assessed primarily through **Progression Free Survival (PFS)**, evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR). Secondary endpoints include **Objective Response (OR)**, **Overall Survival (OS)**, **Duration of Response (DOR)**, and the number of participants experiencing adverse events or discontinuing treatment due to adverse events, all assessed by BICR.

Measurements will be conducted at specified intervals throughout the trial, with the primary focus on comparing the efficacy of MK-7684A, both alone and in combination with docetaxel, against docetaxel monotherapy in participants with metastatic non-small cell lung cancer. The trial will utilize computed tomography (CT) or magnetic resonance imaging (MRI) to identify measurable lesions, ensuring adherence to RECIST 1.1 criteria. The trial is designed to provide a comprehensive evaluation of the treatment's impact on disease progression and patient outcomes.