Phase II Evaluation of Atezolizumab with Platinum and Etoposide in Advanced Large-Cell Neuroendocrine Carcinoma of the Lung in Non-Curative Patients

The primary objective of this Phase II, single-arm trial is to evaluate the **efficacy** of Atezolizumab in addition to standard of care (SoC) chemotherapy for the treatment of advanced large-cell neuroendocrine cancer of the lung (LCNEC). This is measured by overall survival (OS), which is a critical endpoint in assessing the potential benefit of the treatment regimen in extending the life expectancy of patients with this aggressive form of lung cancer.

Secondary objectives include:

• Assessing the **safety** and tolerability of Atezolizumab when combined with SoC, which is essential for determining the feasibility of this treatment approach in a clinical setting.
• Evaluating the **efficacy** of Atezolizumab in addition to SoC by measuring response rate, duration of response (DoR), and progression-free survival (PFS) according to standard and immunotherapy-specific response criteria. These metrics provide a comprehensive understanding of the treatment's impact on disease progression and patient response.

The clinical trial involves **male and female adult patients** diagnosed with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung, who are not eligible for curative treatment. The study population includes individuals aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status ranging from 0 to 2, indicating a general health status that allows for participation in clinical trials. Participants must have measurable disease according to RECIST v1.1 and adequate organ function. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Selection criteria include patients who have not previously received systemic therapy, although those who have relapsed after curative radio chemotherapy or adjuvant chemotherapy are eligible if the relapse occurs at least six months after the discontinuation of curative treatment. The trial population is planned to receive standard of care chemotherapy with Carboplatin or Cisplatin and Etoposide. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is a **Phase II**, single-arm study designed to evaluate the efficacy of **Atezolizumab** in combination with standard chemotherapy, including **Cisplatin**, **Carboplatin**, and **Etoposide**, for the treatment of advanced large-cell neuroendocrine carcinoma of the lung. The primary objective is to assess the overall survival of participants receiving this treatment regimen. The trial is expected to run from January 18, 2022, to January 31, 2029, with participant involvement lasting up to 48 weeks, depending on the treatment regimen.

The trial employs a single-arm design, meaning all participants will receive the investigational treatment without a control group. Participants will be adults with locally advanced or metastatic large-cell neuroendocrine carcinoma of the lung, who are not eligible for curative treatment. The inclusion criteria require participants to have measurable disease according to RECIST v1.1, adequate organ function, and an ECOG performance status of 0-2. Exclusion criteria are not specified in the provided data.

Study visits will follow a structured sequence, beginning with a screening visit to confirm eligibility based on the inclusion criteria. Following successful screening, participants will commence treatment with the investigational regimen. Regular follow-up visits will be scheduled to monitor treatment response, adverse events, and overall health status. These visits will include assessments of objective response rate, disease control rate, progression-free survival, and duration of response, among other secondary endpoints. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they choose to withdraw consent. The trial will also monitor the incidence, nature, and severity of adverse events, graded according to NCI CTCAE v5.0. The study aims to provide valuable insights into the efficacy and safety of the treatment regimen for this specific patient population.

The clinical trial involves the administration of **Atezolizumab**, marketed as Tecentriq, which is a concentrate for solution for infusion. Atezolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF05. It is administered via **intravenous infusion** at a dosage of 1200 mg per administration. The maximum total dose over the course of the trial is 42,000 mg, with a treatment period extending up to 48 weeks. This medication is provided by Roche Registration GmbH and is not a pediatric formulation.

**Cisplatin** is another experimental medication used in this trial. It is a chemical substance administered as a pharmaceutical form PHF00015MIG. The route of administration is **intravenous infusion**, with a maximum daily dose of 80 mg/m² and a total dose not exceeding 320 mg/m² over a 12-week period. Cisplatin is classified under the ATC code L01XA01 and is used as a cytostatic agent in this study.

**Carboplatin** is also included in the trial as a cytostatic agent. It is administered in the pharmaceutical form PHF00230MIG via **intravenous infusion**. The maximum daily dose is 5 units, with a total dose limit of 20 units over a 12-week period. Carboplatin is classified under the ATC code L01XA02 and is not formulated for pediatric use.

**Etoposide** is the third cytostatic agent used in this trial. It is administered in the pharmaceutical form PHF675 through **intravenous infusion**. The maximum daily dose is 100 mg/m², with a total dose not exceeding 1200 mg/m² over a 12-week period. Etoposide is classified under the ATC code L01CB01 and is also not a pediatric formulation.

All medications are administered as part of a combination therapy aimed at evaluating the efficacy of Atezolizumab in addition to standard-of-care chemotherapy for the treatment of advanced large-cell neuroendocrine cancer of the lung. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.

The efficacy of the treatment regimen in this clinical trial will be primarily assessed by measuring **Overall Survival (OS)**, which is defined as the time from cycle 1 day 1 (C1D1) to death from any cause. This serves as the primary endpoint for evaluating the efficacy of Atezolizumab in combination with standard of care chemotherapy for the treatment of advanced large-cell neuroendocrine cancer of the lung (LCNEC).

Secondary endpoints include the **Objective Response Rate (ORR)**, which is defined as the rate of partial remission (PR) or complete remission (CR) according to RECIST v1.1 criteria. Additionally, the **Immune Objective Response Rate (iORR)** will be assessed, defined as immune PR (iPR) or immune CR (iCR) according to iRECIST. The **Disease Control Rate (DCR)**, which combines CR, PR, and stable disease (SD) according to RECIST v1.1, will also be evaluated. **Progression-Free Survival (PFS)** and **Immune Progression-Free Survival (iPFS)** will be measured from C1D1 to progression or death, whichever occurs first, according to RECIST v1.1 and iRECIST, respectively. The **Duration of Response (DoR)** will be calculated from the first documented PR or CR to disease progression or death. Additional assessments include the PFS/iPFS rate at 1 year, OS rate at 1 year, and the incidence, nature, and severity of adverse events graded according to NCI CTCAE v5.0.