Phase III Randomized, Double-Blind Study Comparing Efficacy and Safety of SB27 and Pembrolizumab in Metastatic Non-Squamous Non-Small Cell Lung Cancer

The primary objective of this Phase III randomized, double-blind, multicenter study is to demonstrate the **equivalence** in efficacy of SB27, a proposed pembrolizumab biosimilar, to Keytruda in terms of the objective response rate (ORR) in subjects with metastatic non-squamous non-small cell lung cancer (**NSCLC**). Establishing equivalence in ORR is clinically relevant as it may provide an alternative therapeutic option for patients with metastatic NSCLC, potentially impacting treatment accessibility and cost-effectiveness. No secondary objectives are specified in the study details.

The clinical trial involves a total of **513 participants** diagnosed with **non-small cell lung cancer** (NSCLC), specifically the metastatic non-squamous type. The study population includes both male and female subjects who are 18 years of age or older. Participants have been diagnosed with stage IV non-squamous NSCLC and have not received any prior systemic anti-cancer therapy for metastatic NSCLC. The trial population was selected based on these criteria, and all participants have agreed to use adequate methods of contraception. The study does not specify any particular lifestyle considerations such as diet or physical activity. Both genders are included, and the trial involves a vulnerable population, although specific details about this aspect are not provided. The selection process ensures a diverse representation of individuals who meet the inclusion criteria, contributing to the robustness of the study's findings.

The clinical trial is a **Phase III**, randomized, double-blind, multicenter study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of SB27, a proposed **pembrolizumab** biosimilar, compared to Keytruda in subjects with metastatic non-squamous non-small cell lung cancer (NSCLC). The trial aims to demonstrate the equivalence in efficacy of SB27 to Keytruda, with the primary endpoint being the objective response rate (ORR). The study is expected to commence recruitment on February 19, 2024, and conclude by August 2, 2027.

Participants will be randomly assigned to receive either SB27 or Keytruda, both administered via **intravenous administration**. The trial will include several key visits: an initial screening visit to confirm eligibility based on criteria such as age (≥18 years), diagnosis of stage IV non-squamous NSCLC, and no prior systemic anti-cancer therapy for metastatic NSCLC. Following randomization, participants will undergo regular follow-up visits to monitor treatment response and safety. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.

The expected duration of participant involvement is up to 100 weeks, depending on individual response and tolerance to the treatment. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial is structured to ensure rigorous monitoring and data collection to support the evaluation of the biosimilar's equivalence to the reference product.

**Pemetrexed** is utilized in this clinical trial as a **concentrate for solution for infusion**. The active substance, pemetrexed, is of chemical origin. The medication is administered via **intravenous administration**. The dosage is calculated based on body surface area, with a maximum daily dose of 500 mg/m² and a total maximum dose of 16,500 mg/m² over a treatment period of up to 96 weeks. This medication is not a pediatric formulation and is used as an auxiliary treatment in the trial.

**Keytruda** (pembrolizumab) is another investigational product in this study, provided as a **25 mg/mL concentrate for solution for infusion**. Pembrolizumab is a protein-based substance, specifically classified as "Protein - Other". It is administered intravenously, with a maximum daily dose of 200 mg and a total maximum dose of 6,600 mg over a treatment period of up to 100 weeks. Keytruda serves as a comparator treatment in the trial, with its efficacy being compared to the proposed pembrolizumab biosimilar, SB27.

**Carboplatin** is included in the trial as a **concentrate for solution for infusion**. The active substance, carboplatin, is of chemical origin. It is administered via intravenous administration, with a maximum daily dose of 750 mg and a total maximum dose of 3,000 mg over a treatment period of up to 9 weeks. Carboplatin is used as an auxiliary treatment in the study.

The investigational product **SB27**, a proposed pembrolizumab biosimilar, is also a **concentrate for solution for infusion**. Like Keytruda, it contains pembrolizumab, a protein-based substance. SB27 is administered intravenously, with a maximum daily dose of 200 mg and a total maximum dose of 6,600 mg over a treatment period of up to 100 weeks. SB27 is the test product in this trial, with its efficacy being evaluated against Keytruda in subjects with metastatic non-squamous non-small cell lung cancer.

The efficacy of the clinical trial will be assessed by comparing the **objective response rate (ORR)** between the proposed pembrolizumab biosimilar, SB27, and the reference product, Keytruda, in subjects with metastatic non-squamous non-small cell lung cancer (NSCLC). The primary endpoint for evaluating efficacy is the ORR, which measures the proportion of patients who experience a predefined reduction in tumor size. This endpoint is critical for demonstrating the equivalence in efficacy between the biosimilar and the reference product.