A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy plus Nivolumab versus Neoadjuvant Chemotherapy plus Placebo, followed by Surgical Resection and Adjuvant Treatment with Nivolumab or Placebo for Participants with Resectable Stage II-IIIB Non-small Cell Lung Cancer (CheckMate 77T, CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 77T)

The primary objective of this study is to compare the **event-free survival (EFS)** by blinded independent central review (BICR) in participants with resectable Stage II-IIIB non-small cell lung cancer receiving neoadjuvant chemotherapy plus nivolumab versus those receiving neoadjuvant chemotherapy plus placebo. This objective is clinically relevant as it aims to determine the efficacy of nivolumab in prolonging the period during which patients remain free from cancer-related events, which is crucial for improving long-term outcomes in this patient population.

Secondary objectives include:

• Comparing the overall survival (OS) between the two treatment arms, which is vital for assessing the long-term benefits of the treatment.
• Assessing the pathologic complete response (pCR) rate by BIPR, which provides insights into the treatment's ability to eradicate detectable cancer at the time of surgery.
• Evaluating the major pathological response (MPR) rate by BIPR, which helps in understanding the extent of tumor reduction before surgery.
• Assessing safety and tolerability, which is essential for determining the treatment's feasibility and patient quality of life.

The clinical trial involves a total of **498 participants** diagnosed with **resectable Stage II-IIIB 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 includes adults and older adults. Participants were selected based on specific criteria, including having suspected or histologically confirmed Stage IIA (> 4 cm) to IIIB (T3N2) non-small cell lung carcinoma that is considered resectable, no presence of brain metastasis, and being treatment-naive for NSCLC. Additionally, participants must have the ability to provide surgical or biopsy tumor tissue for biomarker analysis and possess an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1. The trial also includes a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed. The selection process ensures a comprehensive representation of the target demographic for evaluating event-free survival (EFS) by blinded independent central review (BICR) in the study's comparative arms.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of neoadjuvant chemotherapy combined with **nivolumab** versus chemotherapy with a placebo in patients with resectable Stage II-IIIB non-small cell lung cancer. The trial aims to assess the **event-free survival** (EFS) as the primary endpoint, with secondary endpoints including overall survival, pathologic complete response rate, major pathological response rate, and the incidence of serious adverse events. The trial is expected to span from November 2019 to April 2027, with participant involvement lasting up to 64 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as the absence of brain metastasis, treatment-naive status for non-small cell lung cancer, and an ECOG Performance Status of ≤ 1. Following the screening, participants will be randomized to receive either the investigational treatment or the control. The treatment phase will include regular follow-up visits to monitor safety and efficacy, with assessments conducted by blinded independent central review. The end-of-study visit will conclude the participant's involvement, where final evaluations will be performed.

Participants may be withdrawn from the study prematurely if they experience unacceptable toxicity, withdraw consent, or if the investigator deems it in the participant's best interest. The trial will utilize intravenous administration of the study drugs, with **cisplatin**, **carboplatin**, **paclitaxel**, **docetaxel**, and **pemetrexed** being part of the chemotherapy regimen. The study is not categorized as low intervention and is conducted under rigorous scientific and ethical standards to ensure the validity and reliability of the results.

The clinical trial involves the administration of several **experimental medications** and comparator treatments. **Cisplatin Teva® 1 mg/ml** is a concentrate for the preparation of an infusion solution, containing the active substance **cisplatin**. It is administered intravenously with a maximum daily dose of 75 mg/m² and a total dose of 300 mg/m² over a treatment period of 12 weeks. The pharmaceutical form is an injection, and the product is of chemical origin.

**Carboplatin Bendalis 10 mg/ml** is another concentrate for infusion, containing **carboplatin** as the active ingredient. It is also administered intravenously, with a maximum daily dose of 6 mg and a total dose of 24 mg over 12 weeks. The pharmaceutical form is a solution for infusion, and it is of chemical origin.

**Paclitaxel Aurobindo 6 mg/ml** and **Bendatax 6 mg/ml** are both solutions for infusion containing **paclitaxel**. These are administered intravenously with a maximum daily dose of 200 mg/m² and a total dose of 800 mg/m² over 12 weeks. Both products are of chemical origin.

**ALIMTA 500 mg** is a powder for concentrate for solution for infusion, containing **pemetrexed**. It is administered intravenously with a maximum daily dose of 500 mg/m² and a total dose of 2000 mg/m² over 12 weeks. The product is of chemical origin.

**Doce NC 10 mg/ml** and **Docetaxel-Ebewe 10 mg/ml** are concentrates for infusion containing **docetaxel**. These are administered intravenously with a maximum daily dose of 75 mg/m² and a total dose of 300 mg/m² over 12 weeks. Both products are of chemical origin.

**OPDIVO 10 mg/mL** is a concentrate for solution for infusion containing **nivolumab**. It is administered intravenously with a maximum daily dose of 480 mg and a total dose of 7680 mg over a treatment period of 64 weeks. This product is of biological/biotechnological origin.

Non-experimental treatments include **5% Dextrose Solution for Injection** and **0.9% Sodium Chloride Solution for Injection**, which serve as placebo or comparator treatments. These solutions are used to maintain blinding in the study and are not associated with any active pharmaceutical ingredient.

Participant compliance is monitored through regular assessments and documentation of dosing schedules. The trial ensures adherence to the specified dosing regimens and administration routes to maintain the integrity of the study outcomes.

Efficacy in this clinical trial will be assessed primarily through the measurement of **Event-Free Survival (EFS)**, as evaluated by a Blinded Independent Central Review (BICR). This primary endpoint is designed to compare the EFS between participants receiving neoadjuvant chemotherapy plus nivolumab and those receiving neoadjuvant chemotherapy plus placebo. Secondary endpoints include Overall Survival (OS), Pathologic Complete Response (pCR) Rate, and Major Pathological Response (MPR) Rate, all assessed by Blinded Independent Pathology Review. Additionally, the incidence of Serious Adverse Events (SAEs) and Adverse Events (AEs) will be monitored.

The trial involves participants with resectable Stage II-IIIB Non-small Cell Lung Cancer (NSCLC). The efficacy parameters will be collected and analyzed at various stages throughout the trial, with specific timepoints not detailed in the provided data. The trial is structured as a Phase 3, randomized, double-blind study, ensuring rigorous assessment of the treatment's efficacy. The trial is expected to conclude by April 2027, with recruitment having started in November 2019.