eVOLVE-Lung02: A Global Study of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for Participants With Metastatic Non-small Cell Lung Cancer.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05984277
• Collaborator: (none)
• Enrollment: 900
• Locations: 52
• Arms: 2
• Anticipated Duration (Months): 65.5
• Patients Per Site: 17.3
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of eVOLVE-Lung02 is to test the effectiveness (efficacy) and measure the safety of volrustomig in combination with chemotherapy compared with pembrolizumab in combination with chemotherapy as 1L treatment in participants with mNSCLC in PD-L1 < 50%.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Non-small Cell Lung Cancer	Drug: Volrustomig; Drug: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pemetrexed	Phase 3

Detailed Description

Adult patients with a histologically or cytologically documented metastatic NSCLC, with tumors that lack activating EGFR, ALK, and ROS1 alterations are eligible for enrollment. Patients will be randomized in a 1:1 ratio to receive treatment with volrustomig + chemotherapy or pembrolizumab + chemotherapy. Tumor evaluation scans will be performed until disease progression as efficacy assessment. All patients will be followed for survival until the end of the study. An data monitoring committee (DMC) composed of independent experts will be convened to confirm the safety and tolerability of the proposed dose and schedule.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Two-Arm, Parallel, Randomized, Multi-Center, Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer (mNSCLC).
• Anticipated Study Start Date: Nov 30, 2023
• Anticipated Primary Completion Date: May 30, 2028
• Anticipated Study Completion Date: May 16, 2029

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Volrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion	Drug: Volrustomig; Volrustomig; Drug: Carboplatin; Carboplatin; Drug: Paclitaxel; Paclitaxel; Drug: Pemetrexed; Pemetrexed
Active Comparator: Arm 2 Pembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion	Drug: Pembrolizumab; Pembrolizumab; Drug: Carboplatin; Carboplatin; Drug: Paclitaxel; Paclitaxel; Drug: Pemetrexed; Pemetrexed

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) (using BICR assessments according to RECIST 1.1) [Up to approximately 6 years]

   PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression), in PD-L1-negative participants.

2. Overall Survival (OS), in PD-L1-negative participants. [Up to approximately 6 years]

   OS is defined as the time from randomization until the date of death due to any cause, in PD-L1-negative participants.

Secondary Outcome Measures

1. PFS (using BICR assessments according to RECIST 1.1) [Up to approximately 6 years]

   PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by BICR, or death due to any cause (in the absence of progression). The analysis will include all randomized participants.

2. OS [Up to approximately 6 years]

   OS is defined as the time from randomization until the date of death due to any cause. The analysis will include all randomized participants.

3. PFS (using Investigator assessments according to RECIST 1.1) [Up to approximately 6 years]

   PFS is defined as the time from randomization until radiological progression per RECIST 1.1 as assessed by investigator, or death due to any cause (in the absence of progression).

4. Overall Response Rate (ORR) [Up to approximately 6 years]

   ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, as determined by BICR assessments using RECIST 1.1.

5. Duration of Response (DoR) [Up to approximately 6 years]

   DoR is defined as the time from the date of first documented response until the date of documented progression per BICR assessments using RECIST 1.1 or death due to any cause (in the absence of progression). These analyses will include participants who have a confirmed response.

6. PFS2 [Up to approximately 6 years]

   PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial investigator-assessed progression) after the start of the first subsequent therapy, or death. The date of second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice.

7. Concentration of volrustomig in serum and PK parameters [Up to approximately 6 years]

   To assess the PK of volrustomig

8. Presence of ADAs against volrustomig in serum [Up to approximately 6 years]

   To investigate the immunogenicity of volrustomig.

9. Time-To-Deterioration (TTD) in physical functioning [Up to approximately 6 years]

   To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.

10. TTD of lung cancer symptoms [Up to approximately 6 years]

    To assess participant-reported pulmonary symptoms of mNSCLC in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Histologically or cytologically documented squamous or non-squamous NSCLC.

• Stage IV NSCLC (according to Version 8 of the IASLC Staging Manual in Thoracic Oncology 2016), not amenable to curative surgery or radiation.

• Absence of sensitizing EGFR mutations and ALK and ROS1 rearrangements.

• Absence of documented tumor genomic alteration results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved targeted first-line therapies.

Key Exclusion Criteria:

• Mixed small-cell lung cancer and NSCLC histology or sarcomatoid variant. Rare subtypes are excluded.

• Spinal cord compression.

• Brain metastases unless asymptomatic, stable, and not requiring steroids for at least 14 days prior to start of study intervention. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.

• History of another primary malignancy except for:

1. Malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention and of low potential risk for recurrence.

2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.

3. Adequately treated carcinoma in situ without evidence of disease.

• As judged by the investigator, any condition that would interfere with evaluation of the study intervention or interpretation of participant safety or study results.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Rosario		Argentina	S2000DEJ
2	Research Site	Linz		Austria	4021
3	Research Site	Calgary	Alberta	Canada	T2N 4N2
4	Research Site	Halifax	Nova Scotia	Canada	B3H 1V7
5	Research Site	Barrie	Ontario	Canada	L4M 6M2
6	Research Site	Toronto	Ontario	Canada	M4N 3M5
7	Research Site	Lévis	Quebec	Canada	G6V 0B8
8	Research Site	Chengdu		China	611135
9	Research Site	Bergamo		Italy	24125
10	Research Site	Catanzaro		Italy	88100
11	Research Site	Milano		Italy	20162
12	Research Site	Padova		Italy	35128
13	Research Site	Parma		Italy	43126
14	Research Site	Fukuoka-shi		Japan	812-8582
15	Research Site	Kashiwa		Japan	277-8577
16	Research Site	Koto-ku		Japan	135-8550
17	Research Site	Osakasayama-shi		Japan	589-8511
18	Research Site	Cheongju-si		Korea, Republic of	28644
19	Research Site	Jinju-si		Korea, Republic of	52727
20	Research Site	Seoul		Korea, Republic of	03080
21	Research Site	Seoul		Korea, Republic of	06351
22	Research Site	Seoul		Korea, Republic of	06591
23	Research Site	Suwon		Korea, Republic of	16247
24	Research Site	Amsterdam		Netherlands	1081 HV
25	Research Site	Groningen		Netherlands	9728 NT
26	Research Site	Nieuwegein		Netherlands	3435 CM
27	Research Site	Tilburg		Netherlands	5042AD
28	Research Site	Lublin		Poland	20-954
29	Research Site	Przemysl		Poland	37-700
30	Research Site	Rzeszów		Poland	35-241
31	Research Site	Szklarska Poręba		Poland	58-580
32	Research Site	Tomaszów Mazowiecki		Poland	97-200
33	Research Site	Toruń		Poland	87-100
34	Research Site	Warszawa		Poland	01-138
35	Research Site	Warszawa		Poland	02-781
36	Research Site	Łódź		Poland	90-549
37	Research Site	Alicante		Spain	03010
38	Research Site	Barcelona		Spain	08003
39	Research Site	Barcelona		Spain	08025
40	Research Site	Bilbao (Vizcaya)		Spain	48013
41	Research Site	Madrid		Spain	28040
42	Research Site	Málaga		Spain	29011
43	Research Site	Palma		Spain	07198
44	Research Site	Taipei City		Taiwan	110
45	Research Site	Birmingham		United Kingdom	B9 5SS
46	Research Site	Blackpool		United Kingdom	FY3 8NR
47	Research Site	Bury St Edmunds		United Kingdom	IP332QZ
48	Research Site	Colchester		United Kingdom	CO4 5JL
49	Research Site	London		United Kingdom	EC1A 7BE
50	Research Site	London		United Kingdom	NW3 2QG
51	Research Site	London		United Kingdom	SW10 9NH
52	Research Site	Truro		United Kingdom	TR1 3LJ

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT05984277
• Other Study ID Numbers: D798AC00001; 2023-000056-38
• First Posted: Aug 9, 2023
• Last Update Posted: Aug 9, 2023
• Last Verified: Jul 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: metastatic non-small cell lung cancer; non-squamous tumors; squamous tumors; PD-L1
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed

Study Results

No Results Posted as of Aug 9, 2023