A Phase III Randomized, Open-Label, Multi-Center Study of Durvalumab (MEDI4736) Versus Standard of Care (SoC) Platinum-Based Chemotherapy as First Line Treatment in Patients With PD-L1-High Expression Advanced Non Small-Cell Lung Cancer

Brief Summary

Detailed Description

Patients with stage IV NSCLC will be randomized in a 1:1 ratio to 2 treatment arms (durvalumab or SOC therapy). The dual primary objectives of this study are to assess the efficacy of durvalumab versus SoC in terms of OS (Overall Survival) in all randomized patients and in patients who are at low risk of EM (early mortality)

Primary Outcomes

Secondary Outcomes

• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• OS in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• APF12 in PD-L1 TC >= 25% LREM Analysis Set(From date of randomization until 12 months)
• APF12 in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization until 12 months)
• OS at 18 Months(From date of randomization till 18 months.)
• OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set(From date of randomization till 18 months)
• OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization till 18 months)
• OS in PD-L1 TC >= 50% Analysis Set(From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
• PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months DCO 27 October 2022))
• PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment(Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months))
• Time From Randomization to Second Progression (PFS2)(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
• Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status(From Baseline and until follow-up period of 57 months)
• PFS2 in PD-L1 TC >= 25% LREM Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
• PFS2 in PD-L1 TC >= 50% LREM Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
• OS at 18 Months in PD-L1 TC >= 50% Analysis Set(From date of randomization till 18 months)
• Alive and Progression-Free at 12 Months (APF12)(From date of randomization until 12 months)
• APF12 in PD-L1 TC >= 50% Analysis Set(From date of randomization until 12 months)
• PFS2 in PD-L1 TC >= 50% Analysis Set(Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months))
• OS at 24 Months(From date of randomization till 24 months)
• OS at 24 Months in PD-L1 TC >= 50% Analysis Set(From date of randomization till 24 months)
• OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set(From date of randomization till 24 months)
• Time to Deterioration of EORTC QLQ-C30(From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
• Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set(From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022))
• Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set(Up to 24 weeks)
• OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set(From date of randomization till 24 months)
• Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)(Baseline and 12 months)
• Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set(Baseline and 12 months)
• Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set(From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022))
• Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)(Baseline and 12 months)
• Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set(Baseline and 12 months)
• Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set(From Baseline and until follow-up period of 57 months)
• Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab(Up to 24 weeks)
• Time to Deterioration of EORTC QLQ-LC13(From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022))