Evaluation of Atezolizumab and Digital Health Solutions on Health Outcomes in Metastatic and Early-Stage Lung and Hepatocellular Carcinomas

The primary objective of this study is to evaluate the **superiority** of the Roche digital patient monitoring (DPM) atezolizumab Module on symptom interference in Cohort A, which includes patients with metastatic non-small cell lung carcinoma (mNSCLC), extensive-stage small-cell lung carcinoma (ES-SCLC), and advanced or unresectable hepatocellular carcinoma (HCC). Additionally, for Cohort B, the study aims to assess the feasibility of combining the Roche DPM Atezolizumab Module with subcutaneous administration of atezolizumab in a home treatment setting for patients with resected Stage IIB-IIIB non-small cell lung carcinoma (NSCLC). These objectives are clinically relevant as they aim to improve patient management and treatment outcomes by leveraging digital health solutions.

The secondary objectives for Cohort A include assessing the impact of the Roche DPM atezolizumab Module on the number of hospitalizations, cumulative days hospitalized due to serious adverse events (SAEs), unscheduled visits to the emergency room or clinic for symptom management, and the incidence, nature, and severity of all anti-cancer treatment-associated adverse events (AEs). Additional analyses will focus on Grade ≥ 3 AEs, SAEs, selected immune-related adverse events, weighted toxicity score (WTS), and any interruption, modification, or discontinuation of the atezolizumab regimen due to AEs. The study will also evaluate changes from baseline in Global Health Status/Quality of Life score (GHS/QoL) using the EORTC IL6 GHS/QoL, EuroQol EQ-5D-5L index-based and visual analogue scale (VAS) instrument, and the mean symptom severity score from the MD Anderson Symptoms Inventory (MDASI) Core Items. Furthermore, the safety of the Roche DPM atezolizumab Module compared with local standard of care (SOC) support will be assessed.

For Cohort B, secondary objectives include evaluating the number of hospitalizations within one day of atezolizumab subcutaneous administration due to SAEs, and the incidence, nature, and severity of all atezolizumab SC-associated AEs graded according to the NCI-CTCAE v5.0, with additional analyses.

The clinical trial involves a total of **145 participants** diagnosed with specific types of lung and liver cancers, including **metastatic non-small cell lung carcinoma (mNSCLC)**, extensive-stage small-cell lung carcinoma (ES-SCLC), and advanced or unresectable hepatocellular carcinoma (HCC) for Cohort A, as well as resected Stage IIB-IIIB non-small cell lung carcinoma (NSCLC) for Cohort B. 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 their diagnosis and performance status, with Cohort A requiring an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, and Cohort B requiring a status of 0 or 1. The trial includes individuals from a vulnerable population, and all participants must have access to an internet-capable device and connection. Lifestyle factors such as diet and physical activity are not specified, but participants must have a life expectancy of at least 12 weeks for Cohort A and a complete resection of the tumor for Cohort B. The selection criteria ensure that participants have the necessary technological access and health status to engage in the study effectively.

The clinical trial is designed to evaluate the impact of digital health solutions on health outcomes and healthcare resource utilization in participants receiving systemic treatment for specific cancer types. The trial is structured as a **randomized**, **controlled**, and **double-blind** study, ensuring the reliability and validity of the results. The trial is expected to run from February 2023 to August 2025, with participant involvement lasting up to 28 weeks, depending on individual treatment cycles and response.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a confirmed diagnosis of **metastatic non-small cell lung carcinoma**, **extensive-stage small-cell lung carcinoma**, or **advanced hepatocellular carcinoma** for Cohort A, and resected Stage IIB-IIIB non-small cell lung carcinoma for Cohort B. The screening visit will also assess the participant's performance status and life expectancy. Following the screening, participants will attend regular follow-up visits to monitor treatment effects, adverse events, and overall health status. These visits will include assessments of symptom interference and quality of life using validated tools such as the MD Anderson Symptom Inventory and the EuroQoL 5-Dimension Questionnaire.

The primary endpoints of the trial include the mean difference in change of the Total Symptom Interference Score at Week 12 from baseline and the adoption of at-home treatment by Cycle 6. Secondary endpoints focus on the number of hospitalizations, unscheduled visits, and the incidence and severity of adverse events related to the treatment and device use. Participants may be withdrawn from the study if they experience severe adverse events, fail to adhere to the study protocol, or withdraw consent. The trial aims to provide valuable insights into the feasibility and effectiveness of integrating digital health solutions with systemic cancer treatments, potentially informing future clinical practices and patient care strategies.

The clinical trial involves the administration of **Atezolizumab**, an experimental medication, under the product name RO5541267. Atezolizumab is provided in the form of a **solution for injection** and is administered via the **subcutaneous** route. The maximum daily dose of Atezolizumab is 1875 mg, with a total maximum dose of 30 g over a treatment period of 28 days. The pharmaceutical formulation is not specifically designed for pediatric use, and the substance is classified as a protein of other origin. The administration of Atezolizumab is intended to be conducted in a home treatment setting, as part of the study's objective to evaluate the feasibility of combining digital patient monitoring with subcutaneous administration.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on the experimental use of Atezolizumab in conjunction with digital health solutions to assess their impact on health outcomes and healthcare resource utilization. Participant compliance with the dosing schedule will be monitored as part of the study protocol to ensure adherence to the treatment regimen.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoints include the mean difference in change from baseline to Week 12 in the participant-reported Total Symptom Interference Score, as measured by the MD Anderson Symptom Inventory (MDASI) Core Items, and the adoption of at-home treatment by Cycle 6. These endpoints will provide insights into the impact of the Roche digital patient monitoring (DPM) atezolizumab Module on symptom interference and the feasibility of at-home treatment settings.

Secondary endpoints will further evaluate efficacy through various parameters, including the number of hospitalizations and cumulative days hospitalized due to serious adverse events (SAEs), unscheduled visits to the emergency room or clinic for symptom management, and the incidence, nature, and severity of all anti-cancer treatment-associated adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. Additional analyses will focus on Grade ≥ 3 AEs, serious adverse events, selected immune-related adverse events, and the weighted toxicity score (WTS). Changes from baseline in Global Health Status/Quality of Life score (GHS/QoL) from the European Organisation for Research and Treatment of Cancer (EORTC) item library 6 (IL6) GHS/QoL, as well as changes in the EuroQoL 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) index-based and visual analogue scale (VAS) instrument, will also be assessed. Furthermore, the incidence and severity of adverse events related to device use and adverse device effects will be monitored, along with the incidence, nature, and severity of all **Atezolizumab** subcutaneous (SC) associated AEs graded according to the NCI-CTCAE v5.0.