Evaluation of Safety and Pharmacokinetics of Intravenous Fixed-Dose Combination of Tiragolumab and Atezolizumab in Advanced, Recurrent, or Metastatic Solid Tumors

The primary objective of this Phase II, single-arm, open-label study is to evaluate the **safety** and tolerability of the intravenous fixed-dose combination (IV FDC) of tiragolumab and atezolizumab in participants with locally advanced, recurrent, or metastatic **solid tumors**. This is clinically relevant as it aims to determine the potential adverse effects and overall acceptability of this combination therapy, which could inform its future use in clinical practice.

Secondary objectives include:

• Characterizing the **pharmacokinetics** of tiragolumab and atezolizumab following administration of the IV FDC, which is essential for understanding the absorption, distribution, metabolism, and excretion of these agents.
• Evaluating the immune response to tiragolumab and atezolizumab following IV FDC administration by measuring anti-tiragolumab and anti-atezolizumab antibodies, which is important for assessing the potential for immunogenicity and its implications on treatment efficacy and safety.

The clinical trial involves a total of **43 participants** diagnosed with **solid tumors**. 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 histologic documentation of locally advanced, recurrent, or metastatic malignancy that is ineligible for definitive local therapy. The trial population is characterized by adequate hematologic and end organ function, and the presence of PD-L1-selected tumors, as determined by the investigational VENTANA® PD-L1 (SP263) IHC assay. Tumor types among participants include esophageal adenocarcinoma (EAC), esophageal squamous cell carcinoma (ESCC), gastric cancer (GC), gastroesophageal junction cancer (GEJ), hepatocellular carcinoma (HCC), melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), squamous cell carcinoma of the head and neck (SCCHN), and urothelial bladder cancer (UBC). Participants are required to have measurable disease per RECIST v1.1 and a life expectancy of at least 12 weeks. The trial also includes a vulnerable population, although specific lifestyle considerations such as diet or physical activity are not detailed in the available data.

The clinical trial is designed to evaluate the **safety** and pharmacokinetics of an intravenous fixed-dose combination of tiragolumab and atezolizumab in participants with locally advanced, recurrent, or metastatic **solid tumors**. This is a Phase II, single-arm, open-label study. The primary objective is to assess the safety and tolerability of the combination therapy, with the primary endpoint being the incidence and severity of adverse events, determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Secondary endpoints include pharmacokinetic parameters such as the area under the concentration-time curve, maximum serum concentration, and minimum serum concentration of the drugs at Cycle 1, as well as the prevalence and incidence of anti-drug antibodies.

The trial is expected to commence recruitment on November 30, 2023, and is estimated to conclude by December 26, 2025. Participants will be involved in the study for a duration that aligns with the trial's timeline, with specific visit schedules determined by the study protocol. The sequence of study visits includes an initial screening visit to confirm eligibility based on criteria such as histologic documentation of malignancy, adequate hematologic and end organ function, and measurable disease per RECIST v1.1. Follow-up visits will be conducted to monitor safety and pharmacokinetic outcomes, with an end-of-study visit to assess final outcomes and gather comprehensive data.

Participants may be subject to early termination from the study if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it necessary for their safety. The study does not include a control group, and all participants will receive the investigational combination therapy. The trial is not categorized as low intervention, and it is not a pediatric formulation. The study is conducted under the sponsorship of Roche Registration GmbH, with the investigational product being a fixed-dose combination of monoclonal antibodies tiragolumab and atezolizumab.

The clinical trial involves the administration of an **experimental medication** consisting of a fixed-dose combination (FDC) of monoclonal antibodies (mAbs) **tiragolumab** and **atezolizumab**. This combination is developed by Roche Registration GmbH (RRG) and is identified by the sponsor product code Ro 753-8483/F01-02. The pharmaceutical form of the medication is an intravenous (IV) formulation, designed for administration in participants with locally advanced, recurrent, or metastatic solid tumors. The dosing schedule and frequency of administration are not specified in the provided data.

**Tiragolumab** is a monoclonal antibody targeting the T-cell immunoreceptor with Ig and ITIM domains (TIGIT). It is a protein-based therapeutic agent, classified under the origin of "Protein - Other." The substance is also known by synonyms such as RO7092284, MTIG7192A, and RO-7092284. The administration of tiragolumab in combination with atezolizumab aims to enhance the immune response against tumor cells.

**Atezolizumab** is another monoclonal antibody included in the fixed-dose combination. It functions as an immune checkpoint inhibitor, targeting the programmed death-ligand 1 (PD-L1) pathway. Like tiragolumab, atezolizumab is a protein-based therapeutic agent. The combination of these two antibodies is intended to provide a synergistic effect in modulating the immune system to combat cancer.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are mentioned in the trial data. The study is designed as a single-arm, open-label trial, focusing on evaluating the safety and pharmacokinetics of the IV FDC of tiragolumab and atezolizumab. Participant compliance monitoring and specific dosing schedules are not detailed in the available information.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoint focuses on the incidence and severity of adverse events, with severity determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). Additionally, the severity of **cytokine release syndrome (CRS)** will be evaluated using the American Society for Transplantation and Cellular Therapy cytokine release syndrome Consensus Grading Scale.

Secondary endpoints include pharmacokinetic parameters such as the area under the concentration-time curve, maximum serum concentration (Cmax), and minimum serum concentration (Cmin) of tiragolumab and atezolizumab at Cycle 1. The study will also assess the prevalence of anti-drug antibodies (ADAs) to tiragolumab and atezolizumab at baseline, as well as the incidence of treatment-emergent ADAs during the study. These parameters will be measured and analyzed at specified time points to evaluate the pharmacokinetic profile and immunogenicity of the fixed-dose combination of tiragolumab and atezolizumab in participants with locally advanced, recurrent, or metastatic solid tumors.