A Phase II, Open-Label, Multicenter, Randomized Study of the Efficacy and Safety of Adjuvant Autogene Cevumeran Plus Atezolizumab and mFOLFIRINOX versus mFOLFIRINOX Alone in Patients with Resected Pancreatic Ductal Adenocarcinoma

The primary objective of this study is to evaluate the **efficacy** of the combination therapy of autogene cevumeran, atezolizumab, and mFOLFIRINOX compared to mFOLFIRINOX alone, based on **disease-free survival** (DFS) following randomization in patients with resected pancreatic ductal adenocarcinoma. This is clinically relevant as improving DFS can potentially lead to better long-term outcomes and survival rates for patients with this aggressive cancer type.

Secondary objectives include:

• Evaluating the efficacy of the combination therapy compared to mFOLFIRINOX alone based on DFS rates at 12, 24, and 36 months, overall survival (OS) after randomization, and OS rates at 3 and 5 years.
• Assessing the safety profile of the combination therapy compared to mFOLFIRINOX alone.

The clinical trial involves a total of **362 participants** diagnosed with **pancreatic ductal adenocarcinoma**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific criteria, including a preoperative diagnosis of resectable pancreatic ductal adenocarcinoma (PDAC) tumor and a histologically confirmed diagnosis of PDAC. The trial includes individuals who have undergone a macroscopically complete resection of PDAC and show an unequivocal absence of disease post-surgery, as assessed by investigators through imaging and clinical findings. The study population is characterized by a vulnerable group, indicating that special considerations are taken into account for their protection. Lifestyle factors such as diet and physical activity are not specified in the available data. The trial does not restrict participation based on gender, allowing for a diverse representation of the affected population. Key inclusion criteria include specific tumor staging and biochemical markers, such as the carbohydrate antigen 19-9 (CA19-9) level, measured prior to the initiation of study treatment.

The clinical trial is designed to evaluate the **efficacy** and safety of adjuvant **Autogene Cevumeran** plus **Atezolizumab** and mFOLFIRINOX compared to mFOLFIRINOX alone in patients with resected **pancreatic ductal adenocarcinoma**. This is a Phase II, open-label, multicenter, randomized study. The primary objective is to assess disease-free survival (DFS) after randomization. Secondary endpoints include overall survival (OS) rates at specified intervals, incidence and severity of adverse events, and changes from baseline in targeted vital signs and clinical laboratory test results. The trial is expected to conclude by April 30, 2025, with recruitment starting on March 18, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a preoperative diagnosis of resectable pancreatic ductal adenocarcinoma, histologically confirmed diagnosis, and specific TNM staging values. The screening will also ensure the absence of disease post-surgery through imaging and biochemical data. Following randomization, participants will attend follow-up visits at regular intervals to monitor treatment effects and safety. The end-of-study visit will occur at the conclusion of the trial or upon early termination.

The expected length of participant involvement is until the trial's estimated end date, unless early termination is warranted. Conditions for early termination include the occurrence of severe adverse events, withdrawal of consent, or any other reason deemed necessary by the investigator. The trial employs a randomized, controlled design to ensure robust and unbiased results, with participants receiving either the investigational combination therapy or the control treatment. The study's methodology is structured to provide comprehensive data on the comparative efficacy and safety of the treatment regimens under investigation.

The clinical trial involves the evaluation of **Autogene Cevumeran**, a gene therapy medicinal product, which is an mRNA-based treatment developed by Genentech, Inc. This investigational product is designed to encode up to 10 neoepitopes defined by patient-tumor-specific mutations. The pharmaceutical form, dosage, route, and frequency of administration are not specified in the provided data. The product is not a paediatric formulation and is used as a test product in the trial.

**Atezolizumab**, marketed by Roche Registration GmbH, is used in combination with Autogene Cevumeran. It is a protein-based therapeutic, specifically an anti-PD-L1 monoclonal antibody, also known as MPDL3280A. The pharmaceutical form, dosage, route, and frequency of administration are not detailed in the provided data. This product is also not a paediatric formulation and serves as a test product in the trial.

The comparator treatment in the study is **mFOLFIRINOX**, a standard chemotherapy regimen for pancreatic ductal adenocarcinoma. It consists of a combination of several chemotherapeutic agents, including 5-Fluorouracil (5-FU), marketed by Accord Healthcare France SAS, and other manufacturers such as Bendalis GmbH and Teva GmbH. The pharmaceutical form, dosage, route, and frequency of administration for mFOLFIRINOX are not specified in the provided data. These products are not paediatric formulations and are used as comparator treatments in the trial.

All products involved in the trial have undergone secondary packaging and labelling for clinical trial use. Participant compliance monitoring and specific dosing schedules are not detailed in the provided data. The trial aims to compare the efficacy of the combination of Autogene Cevumeran and Atezolizumab with mFOLFIRINOX alone in patients with resected pancreatic ductal adenocarcinoma, focusing on disease-free survival as the primary endpoint.

The efficacy of the clinical trial will be assessed primarily through the evaluation of **disease-free survival (DFS)** after randomization. This primary endpoint will provide a measure of the time patients remain free from any signs or symptoms of pancreatic ductal adenocarcinoma following treatment. Secondary endpoints will include overall survival (OS) after randomization, DFS rates at 12, 24, and 36 months, and OS rates at 3 and 5 years. Additionally, the incidence and severity of adverse events will be monitored, with severity determined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) grading scale. Changes from baseline in targeted vital signs and clinical laboratory test results will also be evaluated.

Data collection will occur at specified intervals, with DFS and OS being key metrics assessed at various timepoints throughout the study duration. The trial will employ imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) scans, alongside biochemical data and clinical findings, to ensure comprehensive monitoring of disease status. The trial aims to compare the efficacy of the combination treatment of autogene cevumeran, atezolizumab, and mFOLFIRINOX against mFOLFIRINOX alone in patients with resected pancreatic ductal adenocarcinoma. The study is designed to provide robust data on the potential benefits of the combination therapy in extending DFS and OS in this patient population.