Volrustomig Monotherapy or Combination Chemotherapy in Advanced Solid Tumors: Phase II Study in Unresectable Pleural Mesothelioma and Esophageal Squamous Cell Carcinoma
- Trial ID
- 2025-523947-36-00
- Protocol
- D798MC00002
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to estimate the efficacy of volrustomig as a monotherapy or in combination with other anticancer agents by assessing the confirmed objective response rate (ORR) in participants with advanced or metastatic solid tumors.
The secondary objectives include:
- Estimation of efficacy through the assessment of duration of response (DoR), progression-free survival (PFS), time to response (TTR), and overall survival (OS).
- Evaluation of the pharmacokinetics (PK) of volrustomig.
- Investigation of the immunogenicity of volrustomig.
Participants
This clinical study involves a total of 203 participants diagnosed with either unresectable pleural mesothelioma or esophageal squamous cell carcinoma. The study population includes both male and female patients. Participants are aged 18 years or older and must possess a performance status of 0 or 1 according to the ECOG scale. Inclusion requires measurable disease based on RECIST 1.1 criteria and a life expectancy of at least 12 weeks. Additionally, subjects must demonstrate adequate organ and bone marrow function, a body weight exceeding 35 kg, and the ability to provide a tumor sample for PD-L1 expression assessment. The primary objectives of the investigation are:
- To estimate the effectiveness of volrustomig monotherapy.
- To evaluate the effectiveness of volrustomig in combination with other anticancer agents through the assessment of confirmed objective response rate.
Plans and Procedures
This Phase II, multi-center, master protocol study aims to evaluate the efficacy and safety of volrustomig administered as monotherapy or in combination with anti-cancer agents. The research focuses on participants with advanced/metastatic solid tumors, specifically including sub-studies for unresectable pleural mesothelioma and esophageal squamous cell carcinoma. The primary objective is to estimate effectiveness through the assessment of confirmed objective response rate (ORR). Study interventions may include combinations with cisplatin, paclitaxel, or fluorouracil. Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DOR), and pharmacokinetics (PK). The study design involves a screening process to evaluate PD-L1 expression and other eligibility criteria such as ECOG performance status and measurable disease via RECIST 1.1. The total duration of participant involvement and study completion is estimated to be an average of 4 years. Data collection continues through study completion to monitor adverse events and immunogenicity.
Treatment
Volrustomig is an experimental therapeutic administered as a solution for infusion via intravenous use.
Paclitaxel is an experimental agent administered via intravenous use at a dosage of 00 mg/m2.
Fluorouracil is an experimental medication administered via intravenous use at a dosage of 00 mg.
Cisplatin is an experimental substance administered via intravenous use at a dosage of 00 mg.
Mycophenolate mofetil is an auxiliary treatment administered via the oral route at a dosage of 00 mg.
Infliximab is an auxiliary treatment administered via intravenous use at a dosage of 00 mg.
Efficacy
The primary efficacy endpoint is the confirmed objective response rate (ORR). This is defined as the proportion of participants achieving a confirmed complete response (CR) or a confirmed partial response (PR), as determined by the investigator according to RECIST 1.1. Secondary efficacy parameters include the duration of response (DOR), defined as the time from the first documented confirmed response until documented disease progression or death from any cause. Other secondary endpoints consist of progression-free survival (PFS), time to response (TTR), and overall survival (OS).
Additional assessments involve the disease control rate (DCR), which is the proportion of participants with a best overall response (BOR) of confirmed CR, confirmed PR, or stable disease (SD). The study will evaluate PFS landmarks at 6, 9, and 12 months, as well as the median OS and the OS rate landmark at 12 months. Pharmacokinetic assessments will measure the concentration of volrustomig in the serum, and immunogenicity will be evaluated by the incidence of anti-drug antibodies (ADAs) in the serum. These assessments will be conducted through study completion, with an average duration of 4 years.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥18 at the time of signing the ICF.
- Provision of tumor sample to assess the PD-L1 expression.
- ECOG performance status of 0 or 1.
- Measurable disease according to RECIST 1.1.
- Life expectancy ≥ 12 weeks.
- Adequate organ and bone marrow function.
- Body weight > 35 kg.
- Capable of giving signed informed consent.
Exclusion Criteria
- Spinal cord compression.
- For sub-study 4, brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. For sub-study 5, participants with untreated or progressive brain metastases.
- Have not recovered (ie, ≤ Grade 1 or at baseline) from an AE due to a previously administered anti-cancer therapy.
- For sub-study 4, participants have contraindications to any of the following drugs: 5- FU, paclitaxel and carboplatin
- History of another primary malignancy except for a) Malignancy treated with curative intent with no known active disease ≥2 years before the first dose of study intervention and of low potential risk for recurrence; b) Adequately treated nonmelanoma skin cancer or lentigo maligna, or carcinoma in situ without evidence of disease.
- Any evidence of diseases, and/or history of organ transplant or allogenic stem cell transplant, which makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
- Evidence of the following infections: active infection including tuberculosis; known HIV infection. that is not well controlled; active or uncontrolled HBV or HCV; or active hepatitis A.
- History of active primary immunodeficiency or active or prior documented autoimmune or inflammatory disorders.
- Participants who are candidates for curative therapy.
- Prior exposure to any immune-mediated therapy.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of the study intervention is excluded. The following are exceptions to this criterion: a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intraarticular injection); b) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication or chemotherapy premedication) or a single dose for palliative purpose (eg, pain control).
- For sub-study 4, participants are ineligible if they have received any anti-cancer therapy within 28 days prior to the first dose of study intervention or within 5 half-lives of the respective agent, whichever is longer.
- Any concurrent chemotherapy except study intervention, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment.
- Radiotherapy treatment with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
- Major surgical procedures within 4 weeks prior to the first dose of the study intervention or still recovering from prior surgery.
- Receipt of live attenuated vaccine within 30 days prior to the first dose of the study intervention.
- Participants with a known allergy or hypersensitivity to any study intervention, on any excipients of any study intervention.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 30 Apr 2026 | 24 |
 Italy | Recruiting | 30 Apr 2026 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
INFLIXIMAB | Other | — | INTRAVENOUS USE | 00 | 126 | SUB02681MIG |
MYCOPHENOLATE MOFETIL | Other | — | ORAL | 00 | 126 | SUB03360MIG |
volrustomig | Test | SOLUTION FOR INFUSION | INTRAVENOUS USE | 00 | 24 | PRD10191166 |
FLUOROURACIL | Test | — | INTRAVENOUS USE | 00 | 126 | SUB07721MIG |
PACLITAXEL | Test | — | INTRAVENOUS USE | 00 | 126 | SUB09583MIG |
CISPLATIN | Test | — | INTRAVENOUS USE | 00 | 126 | SUB07483MIG |