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

Study Overview
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Brief Summary
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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%.

Detailed Description
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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.

Official Title
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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).

Conditions
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Metastatic Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Volrustomig
* Drug: Pembrolizumab
* Drug: Carboplatin
* Drug: Paclitaxel
* Drug: Pemetrexed


Participation Criteria
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Eligibility Criteria
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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: 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. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Volrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion | Drug: Volrustomig<br>* Volrustomig<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Pemetrexed<br>* Pemetrexed<br>|
| Active Comparator: Arm 2<br>Pembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion | Drug: Pembrolizumab<br>* Pembrolizumab<br>Drug: Carboplatin<br>* Carboplatin<br>Drug: Paclitaxel<br>* Paclitaxel<br>Drug: Pemetrexed<br>* Pemetrexed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) (using BICR assessments according to RECIST 1.1) | 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. | Up to approximately 6 years | 
| Overall Survival (OS), in PD-L1-negative participants. | OS is defined as the time from randomization until the date of death due to any cause, in PD-L1-negative participants. | Up to approximately 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS (using BICR assessments according to RECIST 1.1) | 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. | Up to approximately 6 years | 
| OS | OS is defined as the time from randomization until the date of death due to any cause. The analysis will include all randomized participants. | Up to approximately 6 years | 
| PFS (using Investigator assessments according to RECIST 1.1) | 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). | Up to approximately 6 years | 
| Overall Response Rate (ORR) | 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. | Up to approximately 6 years | 
| Duration of Response (DoR) | 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. | Up to approximately 6 years | 
| PFS2 | 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. | Up to approximately 6 years | 
| Concentration of volrustomig in serum and PK parameters | To assess the PK of volrustomig | Up to approximately 6 years | 
| Presence of ADAs against volrustomig in serum | To investigate the immunogenicity of volrustomig. | Up to approximately 6 years | 
| Time-To-Deterioration (TTD) in physical functioning | To assess participant-reported physical functioning in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy. | Up to approximately 6 years | 
| TTD of lung cancer symptoms | To assess participant-reported pulmonary symptoms of mNSCLC in participants treated with volrustomig plus chemotherapy and pembrolizumab plus chemotherapy. | Up to approximately 6 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic non-small cell lung cancer, non-squamous tumors, squamous tumors, PD-L1