MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma (eVOLVE-Meso)
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ClinicalTrials.gov Identifier: NCT06097728 |
Recruitment Status :
Recruiting
First Posted : October 24, 2023
Last Update Posted : April 22, 2024
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Condition or disease | Intervention/treatment | Phase |
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Unresectable Pleural Mesothelioma | Drug: Volrustomig Drug: Pemetrexed Drug: Carboplatin Drug: Cisplatin Drug: Nivolumab Drug: Ipilimumab | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 600 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | This is a randomized, open-label, Phase III trial in participants with untreated unresectable pleural mesothelioma. Approximately 600 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. |
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. |
Primary Purpose: | Treatment |
Official Title: | A Phase III, Randomized, Open-Label, Multicenter, Global Study of Volrustomig (MEDI5752) in Combination With Carboplatin Plus Pemetrexed Versus Platinum Plus Pemetrexed or Nivolumab Plus Ipilimumab in Participants With Unresectable Pleural Mesothelioma (eVOLVE-Meso) |
Actual Study Start Date : | November 9, 2023 |
Estimated Primary Completion Date : | March 15, 2027 |
Estimated Study Completion Date : | March 13, 2028 |
Arm | Intervention/treatment |
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Experimental: Volrustomig + Carboplatin + pemetrexed
Volrustomig in combination with carboplatin plus pemetrexed
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Drug: Volrustomig
MEDI5752: Administered as IV infusion
Other Name: MEDI5752 Drug: Pemetrexed Alimta: Administered as IV infusion
Other Name: Alimta Drug: Carboplatin Paraplatin: Administered as IV infusion
Other Name: Paraplatin |
Active Comparator: Investigator's choice of standard care
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.
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Drug: Pemetrexed
Alimta: Administered as IV infusion
Other Name: Alimta Drug: Carboplatin Paraplatin: Administered as IV infusion
Other Name: Paraplatin Drug: Cisplatin Platinol: Administered as IV infusion
Other Name: Platinol Drug: Nivolumab Opdivo: Administered as IV infusion
Other Name: Opdivo Drug: Ipilimumab Yervoy: Administered as IV infusion
Other Name: Yervoy |
- Overall Survival (OS) in experimental arm relative to comparator arm [ Time Frame: up to approximately 52 months ]OS is defined as the time from randomization until the date of death due to any cause.
- Overall Survival (OS) [ Time Frame: up to approximately 52 months ]OS is defined as the time from randomization until the date of death due to any cause.
- Progression Free Survival (PFS) [ Time Frame: up to approximately 52 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 [ Time Frame: 12, 18, 24, 36 months ]Landmarks of OS12, OS18, OS24, and OS36.
- Landmark PFS [ Time Frame: 6, 12, 18, 24 months ]Landmarks of PFS6, PFS12, PFS18, and PFS24
- Overall Response Rate (ORR) [ Time Frame: up to approximately 52 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) [ Time Frame: up to approximately 52 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 [ Time Frame: up to approximately 52 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 [ Time Frame: up to approximately 52 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) [ Time Frame: Up to approximately 52 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) [ Time Frame: Up to approximately 52 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) [ Time Frame: up to approximately 52 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) [ Time Frame: Up to approximately 52 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 [ Time Frame: up to approximately 52 months ]Incidence of Anti-Drug Antibodies against volrustomig.
- Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0 [ Time Frame: Up to approximately 52 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) [ Time Frame: Up to approximately 52 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) [ Time Frame: Up to approximately 52 months ]The concentration of MEDI5752 in serum will be determined (Cmax will be derived).
- The time taken to reach the maximum concentration (Tmax) [ Time Frame: Up to approximately 52 months ]The concentration of MEDI5752 in serum will be determined (Tmax will be derived).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06097728
Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Principal Investigator: | Marjorie G Zauderer, MD | Memorial Slone Kettering (MSK) Cancer Centre, NY | |
Principal Investigator: | Arnaud Scherpereel, MD | Lille University |
Responsible Party: | AstraZeneca |
ClinicalTrials.gov Identifier: | NCT06097728 |
Other Study ID Numbers: |
D7988C00001 2023-000067-32 ( EudraCT Number ) |
First Posted: | October 24, 2023 Key Record Dates |
Last Update Posted: | April 22, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved. |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
Access Criteria: | When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. |
URL: | https://vivli.org/ |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Mesothelioma Pleural Mesothelioma Unresectable Pleural Mesothelioma Advanced pleural mesothelioma |
Mesothelioma Mesothelioma, Malignant Adenoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Mesothelial Lung Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Pleural Neoplasms Lung Diseases |
Respiratory Tract Diseases Carboplatin Nivolumab Pemetrexed Ipilimumab Antineoplastic Agents Antineoplastic Agents, Immunological Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action Enzyme Inhibitors Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors |