Evaluation of Immune Signature Profiling for Predicting Response to Neoadjuvant Atezolizumab, Carboplatin, and Nab-Paclitaxel in Resectable NSCLC

The primary objective of this exploratory study is to assess the **response** in patients with resectable Stage II, IIIA, and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) undergoing neoadjuvant treatment with Atezolizumab in combination with Carboplatin and nab-Paclitaxel prior to curative intent surgery. This evaluation is clinically relevant as it aims to determine the effectiveness of the neoadjuvant immunochemotherapy regimen in improving surgical outcomes and potentially enhancing long-term survival rates in NSCLC patients.

Secondary objectives include:

• Evaluating response by tumor size.
• Evaluating response by PET-activity.
• Evaluating event-free survival.
• Evaluating overall survival.
• Assessing the feasibility to proceed to surgery after neoadjuvant immunochemotherapy.

The clinical trial involves participants diagnosed with **lung cancer**, specifically non-small cell lung cancer (NSCLC) of non-squamous histology. The study population includes both male and female subjects, aged 18 years and older, who are deemed surgically resectable with curative intent. Participants are required to have adequate renal, hepatic, and bone marrow function, as well as sufficient lung and cardiac function for the intended lung resection. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The sponsor has not provided the total number of participants. The selection criteria emphasize the necessity for participants to have radiologically measurable disease and sufficient availability of tissue samples from the primary tumor before the start of neoadjuvant treatment. Lifestyle considerations such as diet and physical activity are not specified, but participants must comply with effective contraception measures if applicable. The trial population includes a vulnerable population, as indicated by the sponsor.

The clinical trial is designed to evaluate the efficacy of neoadjuvant **atezolizumab** in combination with **carboplatin** and **paclitaxel albumin-bound** in patients with resectable Stage II, IIIA, and select IIIB non-squamous non-small cell lung cancer (NSCLC). This is a Phase 4, randomized, double-blind, controlled trial. The trial commenced on February 22, 2021, with an estimated completion date of December 31, 2026. The study involves multiple visits, starting with an inclusion (screening) visit to assess eligibility based on specific criteria, including adequate organ function and histologically confirmed NSCLC. Participants will undergo a series of follow-up visits to monitor response to treatment, adverse events, and overall health status. The end-of-study visit will occur 6 weeks post-surgery to evaluate the primary endpoint, which is the major pathologic response rate.

Participants are expected to be involved in the study for a maximum treatment period of 63 days for **paclitaxel albumin-bound** and 49 days for both **carboplatin** and **atezolizumab**. The trial includes regular assessments of tumor response using RECIST 1.1 criteria and PET activity, as well as evaluations of event-free survival and overall survival over a 24-month follow-up period. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or failure to comply with study protocols. The trial aims to provide insights into the potential of immune signature profiling for predicting treatment response, thereby contributing to personalized treatment strategies in NSCLC.

The clinical trial involves the administration of three experimental medications, each with specific pharmaceutical forms, dosages, and administration routes. The first medication is **Abraxane**, which is a 5 mg/ml powder for dispersion for infusion. The active substance in Abraxane is **paclitaxel albumin-bound**. It is administered via **intravenous infusion**. The maximum daily dose is 100 mg/m², with a total maximum dose of 900 mg/m² over a treatment period of up to 63 days. This medication is classified as a cytostatic agent and is not a pediatric formulation.

The second medication used in the trial is **Carboplatin Kabi**, a 10 mg/ml concentrate for the preparation of an infusion solution. The active substance is **carboplatin**, and it is administered through **intravenous use**. The maximum daily dose is 500 mg, with a total maximum dose of 1500 mg over a treatment period of up to 49 days. Similar to Abraxane, Carboplatin Kabi is also classified as a cytostatic agent and is not formulated for pediatric use.

The third medication is **Tecentriq**, a 1200 mg concentrate for solution for infusion. The active substance is **atezolizumab**, and it is administered via **intravenous infusion**. The maximum daily dose is 1200 mg, with a total maximum dose of 3600 mg over a treatment period of up to 49 days. Tecentriq is not a pediatric formulation and is not classified as an orphan drug.

Throughout the trial, participant compliance with the dosing schedules is monitored to ensure adherence to the treatment protocol. The trial aims to assess the response in patients with non-squamous Non-Small Cell Lung Cancer (NSCLC) undergoing neoadjuvant treatment with these medications before curative intent surgery.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint is the response to neoadjuvant immunochemotherapy with **ATEZOLIZUMAB**, Carboplatin, and nab-Paclitaxel, as determined by the Major Pathologic Response (MPR) rate, which is defined as having ≤10% residual viable tumor cells. This will be evaluated using pathologic regression grading according to the Junker criteria.

Secondary endpoints include the response rate as determined by changes in tumor size and lymph node size according to RECIST 1.1 criteria, as well as changes in PET activity measured by standardized uptake value (SUV). Additionally, event-free survival (EFS) and overall survival (OS) will be calculated from the start of the first cycle of neoadjuvant treatment, with follow-up extending for 24 months after the end of treatment visit. The end of treatment visit is scheduled to occur 6 weeks after surgery. The number of patients attaining surgery as planned will also be recorded as a secondary endpoint.