MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma

Phase 3RecruitingNCT06097728

AstraZeneca825 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

825

Conditions

Unresectable Pleural Mesothelioma

Interventions

VolrustomigDRUG

MEDI5752: Administered as IV infusion

PemetrexedDRUG

Alimta: Administered as IV infusion

CarboplatinDRUG

Paraplatin: Administered as IV infusion

Cisplatin

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (178)

Outcomes

Primary Outcomes

Overall Survival (OS) in experimental arm relative to comparator arm

OS is defined as the time from randomization until the date of death due to any cause.

Time frame: up to approximately 61 months

Secondary Outcomes

Overall Survival (OS)

OS is defined as the time from randomization until the date of death due to any cause.

Time frame: up to approximately 61 months

Progression Free Survival (PFS)

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.

Time frame: up to approximately 61 months

Landmark OS

Landmarks of OS12, OS18, OS24, and OS36.

Time frame: 12, 18, 24, 36 months

Landmark PFS

Landmarks of PFS6, PFS12, PFS18, and PFS24

Time frame: 6, 12, 18, 24 months

Overall Response Rate (ORR)

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.

Time frame: up to approximately 61 months

Duration of Response (DoR)

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.

Time frame: up to approximately 61 months

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Platinol: Administered as IV infusion

NivolumabDRUG

Opdivo: Administered as IV infusion

IpilimumabDRUG

Yervoy: Administered as IV infusion

Research Site

Phoenix, Arizona, United States

WITHDRAWN

Research Site

Duarte, California, United States

WITHDRAWN

Research Site

Santa Rosa, California, United States

RECRUITING

Research Site

Aurora, Colorado, United States

RECRUITING

Research Site

Jacksonville, Florida, United States

RECRUITING

Research Site

Atlanta, Georgia, United States

RECRUITING

Research Site

Chicago, Illinois, United States

RECRUITING

Research Site

Baltimore, Maryland, United States

RECRUITING

Research Site

Rochester, Minnesota, United States

RECRUITING

Research Site

St Louis, Missouri, United States

RECRUITING

...and 168 more locations

PFS2

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.

Time frame: up to approximately 61 months

Patient-reported physical functioning

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.

Time frame: up to approximately 61 months.

Disease-related symptoms using EORTC IL305 (Q1)

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.

Time frame: Up to approximately 61 months.

Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9)

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.

Time frame: Up to approximately 61 months

Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3)

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.

Time frame: up to approximately 61 months

Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8)

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.

Time frame: Up to approximately 61 months

Immunogenicity of volrustomig

Incidence of Anti-Drug Antibodies against volrustomig.

Time frame: up to approximately 61 months

Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0

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).

Time frame: Up to approximately 61 months

Area under the curve (AUC)

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.

Time frame: Up to approximately 61 months

Maximum plasma concentration of the drug (Cmax)

The concentration of MEDI5752 in serum will be determined (Cmax will be derived).

Time frame: Up to approximately 61 months

The time taken to reach the maximum concentration (Tmax)

The concentration of MEDI5752 in serum will be determined (Tmax will be derived).

Time frame: Up to approximately 61 months