A Multicenter, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of FYB206 and Pembrolizumab in Metastatic Non-Squamous NSCLC

The primary objective of this clinical trial is to demonstrate the comparable effectiveness of **FYB206** to **Keytruda** as an add-on treatment to chemotherapy in patients with metastatic non-squamous non-small cell lung cancer (NSCLC). This is clinically relevant as it aims to establish FYB206 as a viable biosimilar alternative to Keytruda, potentially offering similar therapeutic benefits in the management of metastatic NSCLC.

Secondary objectives include:

• Comparing the efficacy of FYB206 to Keytruda based on further clinical endpoints during Part 1.
• Comparing the safety profiles of FYB206 and Keytruda during Part 1.
• Assessing the impact of FYB206 and Keytruda on the immune response of participants during Part 1.
• Determining and comparing the concentration of FYB206 and Keytruda in the blood post-treatment for Part 1 of the trial.

The clinical trial involves a total of **443 participants** diagnosed with **Stage IV non-squamous non-small cell lung cancer (NSCLC)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific inclusion criteria, such as having a histologically or cytologically confirmed diagnosis of metastatic NSCLC, no prior systemic treatment for metastatic disease, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Additionally, participants must not have tumor-activating or sensitizing EGFR mutations or ALK gene rearrangements. The trial includes a vulnerable population, indicating that special considerations are in place to ensure their safety and ethical treatment. Lifestyle factors such as diet, physical activity, and habits are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy, safety, and immunogenicity of FYB206, a biosimilar candidate to Keytruda, in combination with chemotherapy for patients with metastatic non-squamous non-small cell lung cancer (NSCLC). The trial aims to demonstrate the comparable effectiveness of FYB206 to Keytruda, with the primary endpoint being the proportion of participants whose cancer resolves completely or partially after approximately 9 months of treatment. Secondary endpoints include various measures of disease progression, survival, and immunogenicity over the first year of treatment.

The trial will span an estimated duration from June 2024 to December 2027, with participant involvement expected to last up to 24 months. The study will commence with a screening visit to confirm eligibility based on criteria such as a histologically or cytologically confirmed diagnosis of Stage IV non-squamous NSCLC, no prior systemic treatment for metastatic disease, and an ECOG performance status of 0 or 1. Participants will be randomly assigned to receive either FYB206 or Keytruda, both administered as a **solution for infusion** via **intravenous infusion**.

Study visits will be scheduled at regular intervals to monitor treatment response, side effects, and the development of antibodies against the treatments. Follow-up visits will assess the primary and secondary endpoints, including cancer resolution, disease progression, and overall survival. The end-of-study visit will conclude the participant's involvement, with data collected to evaluate the long-term outcomes of the treatment.

Participants may be withdrawn from the study early if they experience significant adverse effects, disease progression, or if they choose to discontinue participation. The trial is not categorized as low intervention and is conducted as a therapeutic confirmatory trial, ensuring rigorous assessment of the investigational product's performance compared to the established treatment.

The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is administered via **intravenous infusion**. The maximum daily dose is 600 mg, with a total maximum dose of 14,000 mg over a treatment period of up to 24 months. Pembrolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02. The product is manufactured by Merck Sharp & Dohme B.V. and is not formulated for pediatric use. The role of KEYTRUDA in this trial is as a comparator to evaluate the efficacy and safety of the test product.

FYB206, a biosimilar candidate to KEYTRUDA, is also utilized in this study. It is presented as a **solution for infusion** and is administered through **intravenous infusion**. The product is developed by Formycon AG and shares the same active substance, pembrolizumab, as KEYTRUDA. The trial aims to demonstrate the comparable effectiveness of FYB206 to KEYTRUDA when used as an add-on treatment to chemotherapy in patients with metastatic non-squamous non-small cell lung cancer. The maximum treatment period for FYB206 is also 24 months. The role of FYB206 in the trial is as the test product, and it is not intended for pediatric use.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the treatment protocol. Both KEYTRUDA and FYB206 are administered under controlled conditions to maintain the integrity of the study and ensure accurate assessment of their therapeutic effects.

The efficacy of the clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the proportion of participants whose cancer resolves completely or partially after approximately 9 months (40 weeks) from the start of treatment. Secondary endpoints include several measures: the proportion of participants whose cancer resolves completely or partially at prespecified timepoints during the first year, the proportion of participants without disease progression or death after one year, and the proportion of participants alive after one year. Additionally, the time for cancer to resolve completely or partially, and the time from cancer resolving until disease progression will be evaluated. Disease progression is defined as significant tumor growth compared to the previous measurement.

Further secondary endpoints involve the identification and monitoring of side effects, vital signs, oxygen levels, laboratory test results, and other health indicators that change during the first year of treatment. The number of participants who develop antibodies against the treatments will be assessed at pre-decided timepoints. The lowest amounts of the drug will be measured 1 hour before the next dose at various points during the first year of treatment. These assessments will provide comprehensive data on the efficacy of the treatment regimen involving **pembrolizumab** as an add-on to chemotherapy in patients with metastatic non-squamous non-small cell lung cancer.