Evaluation of Safety, Tolerability, and Efficacy of Volrustomig with Anticancer Agents in Patients with Solid Tumors: A Phase II Open-label Study

The primary objective of this study is to assess the **safety** and **tolerability** of volrustomig in combination with other anticancer drugs in participants with specified **solid tumors**. Additionally, the study aims to evaluate the efficacy of this combination by assessing the overall response rate (ORR) in participants. The clinical relevance of these objectives lies in determining the potential of volrustomig as a viable treatment option for solid tumors, which could lead to improved patient outcomes and expanded therapeutic options.

Secondary objectives include:

• To further assess the efficacy of volrustomig in combination with other anticancer drugs in participants with specified solid tumors by disease control rate (DCR) at specified weeks, duration of response (DoR), progression-free survival (PFS), and overall survival (OS).
• To assess the serum concentrations of volrustomig and derived pharmacokinetic (PK) parameters.
• To assess the incidence of anti-drug antibodies (ADAs) against volrustomig or other anticancer agents in serum.

The clinical trial involves a total of **120 participants** diagnosed with **solid tumors**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function. Additionally, participants must have a body weight of at least 35 kilograms at screening and randomization. The trial includes individuals with histologically or cytologically documented non-squamous non-small cell lung cancer (NSQ NSCLC) and excludes those with sensitizing epidermal growth factor receptor (EGFR) mutations or other actionable driver oncogenes for which there are locally approved targeted first-line therapies. Participants must have at least one measurable lesion not previously irradiated that can be accurately measured at baseline. The trial population also includes vulnerable groups, ensuring a comprehensive assessment of the safety and efficacy of the investigational treatment.

The clinical trial is designed as a **Phase II, open-label study** to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of **volrustomig** priming regimens in combination with other anticancer agents in participants with solid tumors. The trial will involve a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate organ and bone marrow function. Participants must have a body weight of at least 35 kilograms and a histologically or cytologically documented non-small cell lung cancer (NSCLC) without certain genetic mutations.

The trial will proceed with follow-up visits to monitor the safety and efficacy of the treatment regimen. The primary endpoints include assessing the safety and tolerability of volrustomig in combination with other anticancer drugs, as well as the overall response rate (ORR) defined by the percentage of participants achieving a complete or partial response according to RECIST 1.1 criteria. Secondary endpoints will evaluate the duration of response (DOR), progression-free survival (PFS), overall survival (OS), and pharmacokinetic parameters such as serum and trough concentrations of volrustomig.

The expected duration of participant involvement in the trial is up to 24 months, with the overall trial estimated to conclude by January 16, 2026. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent by the participant. The trial will not be conducted as a low-intervention study, and it is categorized under Phase II clinical trials. The study will not include pediatric formulations, and the investigational product, volrustomig, will be administered via intravenous infusion.

The clinical trial involves the administration of **volrustomig**, an experimental medication, which is a **solution for infusion**. Volrustomig is a human IgG1 monoclonal antibody with an engineered Fc domain targeting PD-1 and CTLA-4, developed by AstraZeneca AB. It is administered via **intravenous infusion**. The dosing schedule for volrustomig is determined based on the study protocol, with a maximum treatment period of 24 weeks. Participant compliance with the dosing regimen is monitored throughout the trial.

In addition to volrustomig, the study includes the administration of **Pemetrexed Accord 25 mg/ml**, a concentrate for solution for infusion, containing the active substance **pemetrexed**. This medication is provided by Accord Healthcare S.L.U. and is administered **intravenously**. The maximum daily dose is 500 mg/m², with a treatment period extending up to 9999 weeks, as per the study requirements.

**Carboplatin Hikma 10 mg/ml** is another non-experimental treatment used in the study. It is a concentrate for solution for infusion, containing the active substance **carboplatin**, provided by Hikma Farmacêutica (Portugal), S.A. The administration route is **intravenous injection**, with a maximum daily dose of 5 mg, and the treatment period can extend up to 9999 weeks.

The study also includes **Mycofit, 250 mg**, hard capsules containing **mycophenolate mofetil**. This medication is provided by Accord Healthcare Polska Sp. z o.o. and is administered **orally**. The maximum daily dose is 3 grams, with a treatment period of up to 9999 weeks.

Lastly, **Remsima 100 mg** powder for concentrate for solution for infusion, containing the active substance **infliximab**, is used in the study. This medication is provided by Celltrion Healthcare Hungary Kft and is administered via **intravenous use**. The maximum daily dose is 5 mg/kg, with a treatment period extending up to 99999 weeks.

The efficacy of the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoint is the Objective Response Rate (ORR), which is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). This will provide a direct measure of the antitumor activity of **volrustomig** in combination with other anticancer agents in participants with specified solid tumors.

Secondary endpoints include Duration of Response (DOR), Progression-Free Survival (PFS), and Overall Survival (OS). DOR is measured from the date of the first documented response until the date of documented progression or death. PFS is defined as the time from randomization or first dose until radiological progression or death. OS is the time from randomization or first dose until death from any cause. Additionally, the trial will assess the serum and trough concentrations of **volrustomig**, as well as the Area Under the Curve (AUC) concentrations when used alone or in combination with other anticancer agents. The incidence of Anti-Drug Antibodies (ADAs) against **volrustomig** or other anticancer agents will also be evaluated. Disease Control Rate (DCR), defined as the percentage of participants with CR, PR, or stable disease (SD), will be another measure of efficacy.