Efficacy and Safety of Atezolizumab Versus Best Supportive Care Post-Adjuvant Cisplatin-Based Chemotherapy in Resected Stage IB-IIIA Non-Small Cell Lung Cancer

The primary objective of this study is to evaluate the **efficacy** of atezolizumab monotherapy compared with best supportive care, as measured by disease-free survival (DFS) in the PD-L1 subpopulation, defined as having ≥1% tumor cell expression by the SP263 IHC assay. This evaluation is conducted within the Stage II-IIIA population, among all randomized patients with Stage II-IIIA non-small cell lung cancer (NSCLC), and in the intent-to-treat (ITT) population. The clinical relevance of this objective lies in determining the potential of atezolizumab to improve DFS, which is a critical endpoint in assessing the effectiveness of cancer therapies, particularly in early-stage NSCLC where long-term survival is a key concern.

Secondary objectives include:

• Evaluating the efficacy of atezolizumab monotherapy compared with best supportive care as measured by overall survival (OS) in the ITT population.
• Assessing 3-year and 5-year DFS rates in the PD-L1 subpopulation within the Stage II-IIIA population, in all randomized patients with Stage II-IIIA NSCLC, and in the ITT population.
• Evaluating DFS in the PD-L1 subpopulation, defined as having ≥50% tumor cell expression by the SP263 IHC assay, in patients with Stage II-IIIA NSCLC.

These secondary objectives aim to provide a comprehensive understanding of the long-term benefits of atezolizumab, further informing its role in the treatment landscape of NSCLC.

The clinical trial involves a total of **819 participants** diagnosed with **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 criteria, including an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a histological or cytological diagnosis of Stage IB-IIIA NSCLC. All participants must have undergone complete resection of NSCLC and be adequately recovered from surgery. The trial includes individuals eligible to receive a cisplatin-based chemotherapy regimen and those with adequate hematologic and end-organ function. The study population is characterized by a diverse range of individuals, including those from vulnerable populations. Lifestyle factors such as diet and physical activity are not specified in the trial data provided. The selection process ensures that participants meet the necessary health and recovery standards to partake in the study.

The clinical trial is designed as a **randomized**, open-label, controlled study to evaluate the efficacy and safety of **atezolizumab** compared to best supportive care following adjuvant **cisplatin**-based chemotherapy in patients with completely resected Stage IB-IIIA **non-small cell lung cancer** (NSCLC). The trial aims to assess disease-free survival (DFS) as the primary endpoint, with secondary endpoints including overall survival (OS) and DFS rates at 3 and 5 years. The study is expected to run from January 2016 to April 2026, with a maximum treatment period of 48 months for atezolizumab and 12 months for the chemotherapy agents.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a histological or cytological diagnosis of Stage IB-IIIA NSCLC. Following successful screening, participants will be randomized to receive either atezolizumab or best supportive care. The treatment phase will include regular follow-up visits to monitor safety, efficacy, and any adverse events. The end-of-study visit will occur after the completion of the treatment period or upon early termination.

The expected length of participant involvement varies, with those receiving atezolizumab potentially participating for up to 48 months, while those receiving chemotherapy agents may be involved for up to 12 months. Conditions that may lead to early termination from the study include disease progression, unacceptable toxicity, or withdrawal of consent. The trial is structured to ensure rigorous monitoring and assessment of outcomes, with the primary objective of determining the impact of atezolizumab on DFS in the specified patient population.

The clinical trial involves the administration of several **chemotherapy** medications, each with specific pharmaceutical forms, dosages, and administration routes. **Vinorelbine** is utilized in this study as a small molecule chemotherapy medication. It is administered intravenously with a maximum daily dose of 30 mg/m² and a total maximum dose of 240 mg/m² over a treatment period of up to 12 weeks. The pharmaceutical form is denoted as PHF00230MIG.

**Atezolizumab**, marketed as Tecentriq, is a protein-based medication used in this trial. It is provided as a concentrate for solution for infusion, with a maximum daily dose of 1200 mg and a total maximum dose of 19200 mg over a treatment period of up to 48 weeks. The administration route is via intravenous infusion. The product is relabeled for clinical trial use, and it is not a pediatric formulation.

**Cisplatin** is another small molecule chemotherapy agent used in the trial. It is administered intravenously with a maximum daily dose of 75 mg/m² and a total maximum dose of 300 mg/m² over a 12-week period. The pharmaceutical form is identified as PHF00015MIG.

**Docetaxel** is included as a small molecule chemotherapy medication, administered intravenously. The maximum daily dose is 75 mg/m², with a total maximum dose of 300 mg/m² over a 12-week treatment period. The pharmaceutical form is PHF00230MIG.

**Pemetrexed disodium** is administered as a small molecule chemotherapy medication in this trial. It is given intravenously with a maximum daily dose of 500 mg/m² and a total maximum dose of 2000 mg/m² over a 12-week period. The pharmaceutical form is PHF00200MIG.

**Gemcitabine hydrochloride** is also used as a small molecule chemotherapy medication. It is administered intravenously with a maximum daily dose of 1250 mg/m² and a total maximum dose of 10000 mg/m² over a 12-week period. The pharmaceutical form is PHF00230MIG.

All medications are administered intravenously, and participant compliance is monitored throughout the trial. The study does not include any pediatric formulations or orphan drug designations. The trial aims to evaluate the efficacy and safety of these treatments in patients with completely resected stage IB-IIIA non-small cell lung cancer.

The efficacy of the clinical trial will be assessed primarily through **disease-free survival (DFS)**, which is defined as the time from randomization to the first occurrence of any of the following events: first recurrence of non-small cell lung cancer (NSCLC), occurrence of a new primary NSCLC, or death from any cause. This primary endpoint will be evaluated by the investigator through an integrated assessment of radiographic data, biopsy sample results (if available), and clinical status.

Secondary endpoints include overall survival (OS), defined as the time from randomization to death from any cause, and DFS rates at 3 years and 5 years in the PD-L1 subpopulation, Stage II-IIIA population, and the intent-to-treat (ITT) population. Additionally, DFS in the PD-L1 subpopulation within patients with Stage II-IIIA NSCLC will be assessed. These endpoints will provide a comprehensive evaluation of the efficacy of atezolizumab monotherapy compared to best supportive care following adjuvant cisplatin-based chemotherapy in patients with completely resected Stage IB-IIIA NSCLC.