MedPath

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

Phase 3
Recruiting
Conditions
Metastatic Non-small Cell Lung Cancer
Interventions
Registration Number
NCT05984277
Lead Sponsor
AstraZeneca
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%.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
900
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.

  • Symptomatic brain metastases. Brain metastases may be treated or untreated, but participants must be asymptomatic and off 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1PaclitaxelVolrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 2PaclitaxelPembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 1CarboplatinVolrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 1PemetrexedVolrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 2PembrolizumabPembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 1VolrustomigVolrustomig plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 2CarboplatinPembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Arm 2PemetrexedPembrolizumab plus histology-specific chemotherapy (carboplatin plus either pemetrexed or paclitaxel) via iv infusion
Primary Outcome Measures
NameTimeMethod
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.

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.

Secondary Outcome Measures
NameTimeMethod
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.

OSUp 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.

Presence of ADAs against volrustomig in serumUp to approximately 6 years

To investigate the immunogenicity of volrustomig.

TTD of lung cancer symptomsUp to approximately 6 years

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

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.

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.

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).

PFS2Up 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.

Concentration of volrustomig in serum and PK parametersUp to approximately 6 years

To assess the PK of volrustomig

Time-To-Deterioration (TTD) in physical functioningUp to approximately 6 years

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

Trial Locations

Locations (1)

Research Site

🇬🇧

Truro, United Kingdom

© Copyright 2025. All Rights Reserved by MedPath