Unresectable Pleural Mesothelioma
Conditions
Keywords
Mesothelioma, Pleural Mesothelioma, Unresectable Pleural Mesothelioma, Advanced pleural mesothelioma
Brief summary
This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed vs the investigator's choice of platinum + Pemetrexed or Nivolumab + Ipilimumab in participants with unresectable pleural mesothelioma.
Detailed description
Adult patients with histologically proven diagnosis of pleural mesothelioma with advanced unresectable disease are eligible to be enrolled. Patients will be randomized 1:1 to receive Volrustomig (MEDI5752) + Carboplatin + Pemetrexed or the investigator's choice of platinum+Pemetrexed or Nivolumab+Ipilimumab, based on their histology.
Interventions
DRUGVolrustomig
MEDI5752: Administered as IV infusion
DRUGPemetrexed
Alimta: Administered as IV infusion
DRUGCarboplatin
Paraplatin: Administered as IV infusion
DRUGCisplatin
Platinol: Administered as IV infusion
DRUGNivolumab
Opdivo: Administered as IV infusion
DRUGIpilimumab
Yervoy: Administered as IV infusion
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
This is an open-label study for the personnel at study sites; the specific treatment to be taken by a participant will be assigned using an Interactive Response Technology/Randomization and Trial Supply Management. To maintain the integrity of the study, AstraZeneca personnel directly involved in the study conduct will not undertake or have access to efficacy data aggregated by treatment arm prior to final data readout for the primary endpoint.
Intervention model description
This is a randomized, open-label, Phase III trial in participants with untreated unresectable pleural mesothelioma. Approximately 825 participants across histology subtypes will be randomized in a 1:1 ratio to receive volrustomig in combination with carboplatin plus pemetrexed or the investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participant must be ≥ 18 years at the time of screening * Histologically proven diagnosis of pleural mesothelioma with known histology (epithelioid vs. non-epithelioid) * Advanced unresectable disease that cannot be treated with curative surgery (with or without chemotherapy) * WHO/ECOG performance status of 0 or 1 with no deterioration (that is, ECOG PS\>1) over the previous 2 weeks prior to day of first dosing * Has measurable disease per modified RECIST1.1 * Has adequate bone marrow reserve and organ function at baseline Key
Exclusion criteria
* As judged by the investigator, any condition that would interfere with evaluation of the investigational product or interpretation of participant safety or study results. * Active or prior documented autoimmune or inflammatory disorders * History of another primary malignancy with exceptions. * Uncontrolled intercurrent illness * Tuberculosis, hepatitis B (HBV) or hepatitis C (HCV), human immunodeficiency virus (HIV) infection that is not well controlled * Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment * Untreated or progressive CNS metastatic disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in experimental arm relative to comparator arm | up to approximately 61 months | OS is defined as the time from randomization until the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | up to approximately 61 months | OS is defined as the time from randomization until the date of death due to any cause. |
| Progression Free Survival (PFS) | up to approximately 61 months | PFS is defined as the time from randomization until progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site, or death due to any cause. |
| Landmark OS | 12, 18, 24, 36 months | Landmarks of OS12, OS18, OS24, and OS36. |
| Landmark PFS | 6, 12, 18, 24 months | Landmarks of PFS6, PFS12, PFS18, and PFS24 |
| Overall Response Rate (ORR) | up to approximately 61 months | Proportion of participants who have a confirmed Complete Response or confirmed Partial Response, as determined by the investigator at local site per mRECIST 1.1 and/or RECIST 1.1. |
| Duration of Response (DoR) | up to approximately 61 months | DoR defined as the time from the date of first documented response until date of documented progression per mRECIST 1.1 and/or RECIST 1.1 as assessed by the investigator at local site or death due to any cause. |
| PFS2 | up to approximately 61 months | PFS2 defined as the time from randomization to the earliest of the progression event (following the initial investigator-assessed progression), after first subsequent therapy, or death. |
| Patient-reported physical functioning | up to approximately 61 months. | TTD in physical functioning as measured by PROMIS (Patient Reported Outcomes Measurement Information System) Physical Function Short Form 8c. There are 8 questions each from a scale of 1 (unable to do) to a scale of 5 (With a little difficulty). The higher the scores the better the patient-reported physical functioning is. |
| Disease-related symptoms using EORTC IL305 (Q1) | Up to approximately 61 months. | Change from baseline in disease-related symptoms as measured by individual symptom items from the EORTC (European Organisation For Research And Treatment Of Cancer) IL305 (Item Library 305) (Q1). It is scored from a 1 (not at all) to a 4 (very much). The higher the score the higher the disease-related symptoms. |
| Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9) | Up to approximately 61 months | Change from baseline in disease-related symptoms as measured by individual symptom items from the PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events) (Q1, 5, 6, 9). PRO-CTCAE responses are scored from 0 to 4 (or 0/1 for absent/present). The higher the score the higher the disease-related symptoms. |
| Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3) | up to approximately 61 months | Change from baseline in functioning will be assessed by the following measure: Role functioning: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 RF (Role Functioning) subscale (IL305 Q2 3) (Item Library 305). The questions are from a scale of 1 (not at all) to 4 (very much). The lower the score the higher the patient-reported role functioning is. |
| Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8) | Up to approximately 61 months | Change from baseline in functioning will be assessed by the following measure: HRQoL: EORTC (European Organisation For Research And Treatment Of Cancer) QLQ (Quality of Life Questionnaire) -C30 HRQoL subscale (IL305 Q7-8) (Item Library 305). The questions are from a scale of 1 (very poor) to 7 (excellent). The higher the score the higher the HRQoL. |
| Immunogenicity of volrustomig | up to approximately 61 months | Incidence of Anti-Drug Antibodies against volrustomig. |
| Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0 | Up to approximately 61 months | Incidence of Adverse Events (AEs) AEs graded by CTCAE (Common Terminology Criteria for Adverse Events) version 5.0. Grade refers to the severity of the AE. The CTCAE displays grade 1 (mild) through 5 (death related to AE). Grade 2 (moderate), Grade 3 (Severe) and Grade 4 (Life-threatening consequences). |
| Area under the curve (AUC) | Up to approximately 61 months | The concentration of MEDI5752 in serum will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered. |
| Maximum plasma concentration of the drug (Cmax) | Up to approximately 61 months | The concentration of MEDI5752 in serum will be determined (Cmax will be derived). |
| The time taken to reach the maximum concentration (Tmax) | Up to approximately 61 months | The concentration of MEDI5752 in serum will be determined (Tmax will be derived). |
Countries
Australia, Belgium, Brazil, Canada, China, Denmark, France, Germany, Italy, Japan, Netherlands, Norway, Poland, South Africa, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
PRINCIPAL_INVESTIGATORMarjorie G Zauderer, MD
Memorial Slone Kettering (MSK) Cancer Centre
PRINCIPAL_INVESTIGATORArnaud Scherpereel, MD
Lille University
Outcome results
None listed