eVOLVE-Meso: MEDI5752 in Combination With Carboplatin Plus Pemetrexed in Unresectable Pleural Mesothelioma

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06097728
• Collaborator: (none)
• Enrollment: 600
• Locations: 134
• Arms: 2
• Anticipated Duration (Months): 52.1
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Study Design

• Study Type: Interventional
• Anticipated 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.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)
• Anticipated Study Start Date: Nov 30, 2023
• Anticipated Primary Completion Date: Apr 5, 2027
• Anticipated Study Completion Date: Apr 3, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Volrustomig + Carboplatin + pemetrexed Volrustomig in combination with carboplatin plus pemetrexed	Drug: Volrustomig; MEDI5752: Administered as IV infusion; Other Names: MEDI5752 ; Drug: Pemetrexed; Alimta: Administered as IV infusion; Other Names: Alimta ; Drug: Carboplatin; Paraplatin: Administered as IV infusion; Other Names: 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 Names: Alimta ; Drug: Carboplatin; Paraplatin: Administered as IV infusion; Other Names: Paraplatin ; Drug: Cisplatin; Platinol: Administered as IV infusion; Other Names: Platinol ; Drug: Nivolumab; Opdivo: Administered as IV infusion; Other Names: Opdivo ; Drug: Ipilimumab; Yervoy: Administered as IV infusion; Other Names: Yervoy

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) in experimental arm relative to comparator arm [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) [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) [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 [12, 18, 24, 36 months]

   Landmarks of OS12, OS18, OS24, and OS36.

4. Landmark PFS [6, 12, 18, 24 months]

   Landmarks of PFS6, PFS12, PFS18, and PFS24

5. Overall Response Rate (ORR) [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) [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 [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 [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) [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) [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) [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) [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 [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 [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) [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) [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) [Up to approximately 52 months]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Duarte	California	United States	91010
2	Research Site	Santa Rosa	California	United States	92805
3	Research Site	Aurora	Colorado	United States	80045
4	Research Site	Chicago	Illinois	United States	60637
5	Research Site	Commack	New York	United States	11725
6	Research Site	Portland	Oregon	United States	97239
7	Research Site	Philadelphia	Pennsylvania	United States	19104
8	Research Site	Fairfax	Virginia	United States	22031
9	Research Site	Clayton		Australia	3168
10	Research Site	Nedlands		Australia	6009
11	Research Site	Anderlecht		Belgium	1070
12	Research Site	Antwerpen		Belgium	2020
13	Research Site	Gent		Belgium	9000
14	Research Site	Hasselt		Belgium	3500
15	Research Site	Leuven		Belgium	3000
16	Research Site	Barretos		Brazil	14784-400
17	Research Site	Fortaleza		Brazil	60336-045
18	Research Site	Joao Pessoa		Brazil	58013-140
19	Research Site	Porto Alegre		Brazil	91350-200
20	Research Site	Rio de Janeiro		Brazil	22281-100
21	Research Site	Santo Andre		Brazil	09060-650
22	Research Site	Sao Paulo		Brazil	01246-000
23	Research Site	Edmonton	Alberta	Canada	T6G 1Z2
24	Research Site	London	Ontario	Canada	N6A 5W9
25	Research Site	Ottawa	Ontario	Canada	K1H 8L6
26	Research Site	Toronto	Ontario	Canada	M5G 1X6
27	Research Site	Montreal	Quebec	Canada	H2X 1P1
28	Research Site	Quebec		Canada	G1V 4G5
29	Research Site	Beijing		China	100142
30	Research Site	Beijing		China	100210
31	Research Site	Changsha		China	410013
32	Research Site	Chengdu		China	610042
33	Research Site	Guangzhou		China	510060
34	Research Site	Guangzhou		China	510180
35	Research Site	Hangzhou		China	310022
36	Research Site	Harbin		China	150049
37	Research Site	Kunming		China	650118
38	Research Site	Lanzhou		China	730000
39	Research Site	Nanchang		China	330006
40	Research Site	Ningbo		China	315100
41	Research Site	Shanghai		China	200032
42	Research Site	Shenyang		China	110044
43	Research Site	Taiyuan		China	030032
44	Research Site	Tianjin		China	300052
45	Research Site	Tianjin		China	300060
46	Research Site	Wuhan		China	430030
47	Research Site	Xi'an		China	710061
48	Research Site	Zhengzhou		China	450008
49	Research Site	Aarhus N		Denmark	8200
50	Research Site	Copenhagen		Denmark	2100
51	Research Site	Brest		France	29200
52	Research Site	Creteil Cedex		France	94010
53	Research Site	Le Mans Cedex		France	72037
54	Research Site	Lille		France	59037
55	Research Site	Lyon		France	69373
56	Research Site	Marseille Cedex 20		France	13015
57	Research Site	Montpellier		France	34298
58	Research Site	Rouen		France	76031
59	Research Site	Saint Herblain		France	44800
60	Research Site	Strasbourg		France	67091
61	Research Site	Toulouse		France	31059
62	Research Site	Berlin		Germany	13125
63	Research Site	Essen		Germany	45130
64	Research Site	Gauting		Germany	82131
65	Research Site	Georgsmarienhuette		Germany	49124
66	Research Site	Heidelberg		Germany	69126
67	Research Site	Köln		Germany	51109
68	Research Site	Münster		Germany	48163
69	Research Site	Alessandria		Italy	15100
70	Research Site	Bari		Italy	70124
71	Research Site	Bergamo		Italy	24125
72	Research Site	Milan		Italy	20141
73	Research Site	Monza		Italy	20052
74	Research Site	Orbassano		Italy	10043
75	Research Site	Padova		Italy	35128
76	Research Site	Parma		Italy	43100
77	Research Site	Rozzano		Italy	20089
78	Research Site	Varese		Italy	21100
79	Research Site	Hiroshima-shi		Japan	734-8551
80	Research Site	Nagoya-shi		Japan	466-8560
81	Research Site	Nishinomiya-shi		Japan	663-8501
82	Research Site	Okayama-shi		Japan	702-8055
83	Research Site	Osakasayama-shi		Japan	589-8511
84	Research Site	Tokyo		Japan	104-0045
85	Research Site	Ube-shi		Japan	755-0241
86	Research Site	Cheongju-si		Korea, Republic of	28644
87	Research Site	Seoul		Korea, Republic of	03080
88	Research Site	Seoul		Korea, Republic of	06351
89	Research Site	Seoul		Korea, Republic of	06591
90	Research Site	Amsterdam		Netherlands	1066CX
91	Research Site	Eindhoven		Netherlands	5623EJ
92	Research Site	Rotterdam		Netherlands	3015 GD
93	Research Site	Lørenskog		Norway	1478
94	Research Site	Oslo		Norway	450
95	Research Site	Bydgoszcz		Poland	85-796
96	Research Site	Bystra		Poland	43-360
97	Research Site	Olsztyn		Poland	10-357
98	Research Site	Poznań		Poland	60-569
99	Research Site	Rzeszów		Poland	35-241
100	Research Site	Warszawa		Poland	02-781
101	Research Site	Amanzimtoti		South Africa	4126
102	Research Site	Johannesburg		South Africa	2013
103	Research Site	Kraaifontein		South Africa	7570
104	Research Site	Parktown		South Africa	2193
105	Research Site	Pretoria		South Africa	0002
106	Research Site	Pretoria		South Africa	0081
107	Research Site	Barakaldo		Spain	48903
108	Research Site	Barcelona		Spain	8035
109	Research Site	Madrid		Spain	28041
110	Research Site	Oviedo		Spain	33011
111	Research Site	Basel		Switzerland	4031
112	Research Site	Basel		Switzerland	CH-5405
113	Research Site	Bern		Switzerland	CH-3010
114	Research Site	Fribourg		Switzerland	1700
115	Research Site	St. Gallen		Switzerland	9007
116	Research Site	Kaohsiung		Taiwan	80756
117	Research Site	Taichung		Taiwan	40705
118	Research Site	Tainan City		Taiwan	70403
119	Research Site	Taipei		Taiwan	10002
120	Research Site	Adana		Turkey	01060
121	Research Site	Ankara		Turkey	06280
122	Research Site	Ankara		Turkey	06800
123	Research Site	Diyarbakir		Turkey	21280
124	Research Site	Izmir		Turkey	35110
125	Research Site	Cambridge		United Kingdom	CB2 0QQ
126	Research Site	Leeds		United Kingdom	LS9 7TF
127	Research Site	Leicester		United Kingdom	LE1 5WW
128	Research Site	London		United Kingdom	NW1 2PG
129	Research Site	London		United Kingdom	SE1 9RT
130	Research Site	Manchester		United Kingdom	M23 9LT
131	Research Site	Middlesbrough		United Kingdom	TS4 3BW
132	Research Site	Newcastle-upon-Tyne		United Kingdom	NE2 4HH
133	Research Site	Portsmouth		United Kingdom	PO6 3LY
134	Research Site	Taunton		United Kingdom	TA1 5DA

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Marjorie G Zauderer, MD, Memorial Slone Kettering (MSK) Cancer Centre, NY
• Principal Investigator: Arnaud Scherpereel, MD, Lille University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT06097728
• Other Study ID Numbers: D7988C00001; 2023-000067-32
• First Posted: Oct 24, 2023
• Last Update Posted: Oct 24, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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: Mesothelioma; Mesothelioma, Malignant; Carboplatin; Nivolumab; Pemetrexed; Ipilimumab

Study Results

No Results Posted as of Oct 24, 2023