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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 : March 26, 2024
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Unresectable Pleural Mesothelioma Drug: Volrustomig Drug: Pemetrexed Drug: Carboplatin Drug: Cisplatin Drug: Nivolumab Drug: Ipilimumab Phase 3

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.

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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
Experimental: Volrustomig + Carboplatin + pemetrexed
Volrustomig in combination with carboplatin plus pemetrexed
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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. Landmark OS [ Time Frame: 12, 18, 24, 36 months ]
    Landmarks of OS12, OS18, OS24, and OS36.

  4. Landmark PFS [ Time Frame: 6, 12, 18, 24 months ]
    Landmarks of PFS6, PFS12, PFS18, and PFS24

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.


  12. 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.


  13. Immunogenicity of volrustomig [ Time Frame: up to approximately 52 months ]
    Incidence of Anti-Drug Antibodies against volrustomig.

  14. 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).

  15. 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.

  16. 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).

  17. 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).



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
Show Show 149 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Marjorie G Zauderer, MD Memorial Slone Kettering (MSK) Cancer Centre, NY
Principal Investigator: Arnaud Scherpereel, MD Lille University
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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: March 26, 2024
Last Verified: March 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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Mesothelioma
Pleural Mesothelioma
Unresectable Pleural Mesothelioma
Advanced pleural mesothelioma
Additional relevant MeSH terms:
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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