Non Small Cell Lung Carcinoma NSCLC
Conditions
Keywords
NSCLC, PD-L1, Durvalumab (MEDI4736), OS
Brief summary
This is a randomized, open-label, multi-center Phase III study to determine the efficacy and safety of durvalumab versus platinum-based SoC chemotherapy in the first-line treatment of advanced NSCLC in patients who are epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type and with PD-L1 high expression (PEARL)
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)
Interventions
Anti-PD-L1 monoclonal Antibody monotherapy
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agent
Chemotherapy Agent
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Aged at least 18 years * Documented evidence of Stage IV NSCLC * No sensitizing EGFR mutation and ALK rearrangement * PD-L1 high expression * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Prior chemotherapy or any other systemic therapy for advanced NSCLC * Prior exposure to immune-mediated therapy, including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines * Brain metastases or spinal cord compression unless the patient is stable and off steroids for at least 14 days prior to start of study treatment * Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant * Active or prior documented autoimmune or inflammatory disorders (e.g., colitis or Crohn's disease\]
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022] | OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. |
| OS in Participants With LREM | From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022) | OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. |
| 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) | OS is defined as the time from the date of randomization until death due to ay cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. |
| 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) | The PFS (per RECIST 1.1) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). Progression of disease per RECIST 1.1, when either 1 of the criteria met: Target lesion (TL): at least a 20% increase in the sum of diameters of TLs, for reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Non-target lesion (NTL): Unequivocal progression of existing NTLs. It may be due to an important progression in 1 lesion only or in several lesions. In all cases the progression must be clinically significant for the physician to consider changing (or stopping) therapy. New lesions: the presence of 1 or more new lesions was assessed as progression. |
| OS at 24 Months in PD-L1 TC >= 50% Analysis Set | From date of randomization till 24 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. |
| 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) | The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). |
| 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) | The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). |
| 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) | The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). |
| 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) | ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs). Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. |
| 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 (per RECIST 1.1 using Investigator assessments)was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. |
| 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) | ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. |
| 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) | ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. |
| 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 (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. |
| 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) | DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. |
| 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) | DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. |
| 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) | DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. |
| Alive and Progression-Free at 12 Months (APF12) | From date of randomization until 12 months | The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. |
| APF12 in PD-L1 TC >= 25% LREM Analysis Set | From date of randomization until 12 months | The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. |
| APF12 in PD-L1 TC >= 50% Analysis Set | From date of randomization until 12 months | The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. |
| APF12 in PD-L1 TC >= 50% LREM Analysis Set | From date of randomization until 12 months | The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. |
| 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) | PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. |
| 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 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. |
| 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) | PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. |
| 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) | PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. |
| OS at 18 Months | From date of randomization till 18 months. | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. |
| OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set | From date of randomization till 18 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. |
| OS at 18 Months in PD-L1 TC >= 50% Analysis Set | From date of randomization till 18 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. |
| OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set | From date of randomization till 18 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. |
| OS at 24 Months | From date of randomization till 24 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. |
| OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set | From date of randomization till 24 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. |
| OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set | From date of randomization till 24 months | OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 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 | The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months. |
| Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Baseline and 12 months | The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 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 symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration (a decrease in the function scales or the global health status/ health-related quality of life \[HRQoL\] from baseline of ≥10) that was confirmed at a subsequent visit or death in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. |
| 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) | Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. |
| Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Baseline and 12 months | The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months. |
| Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Baseline and 12 months | The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months. |
| 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) | Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. |
| 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) | Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. |
| Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | From Baseline and until follow-up period of 57 months | ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported. |
| 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 | ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported. |
| Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab | Up to 24 weeks | Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. |
| Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set | Up to 24 weeks | Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. |
Countries
Australia, China, Hungary, Netherlands, Poland, Russia, South Korea, Taiwan, Thailand, Turkey (Türkiye), United States, Vietnam
Participant flow
Recruitment details
This Phase III, open-label, multi-center study was conducted in participants with programmed cell death ligand 1 (PD-L1)- tumor cell (TC) \>= 25% advanced non small-cell lung cancer (NSCLC) at 85 centers in 10 countries (China, Russia, Hungary, Poland, South Korea, Vietnam, Turkey, Australia, Taiwan, and Thailand). First participant was enrolled on 02 January 2017 and last participant was enrolled on 25 January 2019.
Pre-assignment details
Overall 3075 participants were screened at 98 centers in 12 countries. A total of 669 participants were randomized in a 1:1 ratio. Of those, 549 participants fulfilled the criteria for PD-L1 TC \>= 25% low risk of early mortality (LREM).
Participants by arm
| Arm | Count |
|---|---|
| Durvalumab Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met. | 335 |
| Platinum-based SoC Participants received 1 of the following IV infusion treatment combination platinum-based SoC as per Investigator's choice on Day 1 of each 21-day cycle for 4 to 6 cycles or until documented PD or until specific treatment discontinuation criteria were met.
1. Paclitaxel 175 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions.
2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2 (for squamous participants).
3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 via infusions (for squamous participants).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (for non-squamous participants; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 via IV infusions (for non-squamous participants; pemetrexed maintenance dose was permitted). | 334 |
| Total | 669 |
Baseline characteristics
| Characteristic | Durvalumab | Platinum-based SoC | Total |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 9.73 | 61.9 years STANDARD_DEVIATION 8.71 | 61.3 years STANDARD_DEVIATION 9.25 |
| Race/Ethnicity, Customized Asian | 262 Participants | 273 Participants | 535 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 6 Participants | 8 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 333 Participants | 328 Participants | 661 Participants |
| Race/Ethnicity, Customized White | 73 Participants | 61 Participants | 134 Participants |
| Sex: Female, Male Female | 67 Participants | 65 Participants | 132 Participants |
| Sex: Female, Male Male | 268 Participants | 269 Participants | 537 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 274 / 335 | 277 / 334 |
| other Total, other adverse events | 271 / 335 | 294 / 327 |
| serious Total, serious adverse events | 132 / 335 | 104 / 327 |
Outcome results
Primary
OS in Participants With LREM
OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
Time frame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | OS in Participants With LREM | 14.6 months |
| Platinum-based SoC | OS in Participants With LREM | 15.0 months |
p-value: 0.62895% CI: [0.793, 1.151]Stratified log-rank test
Primary
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
Time frame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]
Population: The FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | Overall Survival (OS) | 14.6 months |
| Platinum-based SoC | Overall Survival (OS) | 12.8 months |
p-value: 0.03795% CI: [0.706, 0.989]Stratified Log-rank test
Secondary
Alive and Progression-Free at 12 Months (APF12)
The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.
Time frame: From date of randomization until 12 months
Population: The FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | Alive and Progression-Free at 12 Months (APF12) | 25.5 percentage of participants |
| Platinum-based SoC | Alive and Progression-Free at 12 Months (APF12) | 13.3 percentage of participants |
Secondary
APF12 in PD-L1 TC >= 25% LREM Analysis Set
The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.
Time frame: From date of randomization until 12 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | APF12 in PD-L1 TC >= 25% LREM Analysis Set | 24.1 percentage of participants |
| Platinum-based SoC | APF12 in PD-L1 TC >= 25% LREM Analysis Set | 16.4 percentage of participants |
Secondary
APF12 in PD-L1 TC >= 50% Analysis Set
The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.
Time frame: From date of randomization until 12 months
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | APF12 in PD-L1 TC >= 50% Analysis Set | 26.1 percentage of participants |
| Platinum-based SoC | APF12 in PD-L1 TC >= 50% Analysis Set | 11.7 percentage of participants |
Secondary
APF12 in PD-L1 TC >= 50% LREM Analysis Set
The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.
Time frame: From date of randomization until 12 months
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | APF12 in PD-L1 TC >= 50% LREM Analysis Set | 26.5 percentage of participants |
| Platinum-based SoC | APF12 in PD-L1 TC >= 50% LREM Analysis Set | 14.5 percentage of participants |
Secondary
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)
The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months.
Time frame: Baseline and 12 months
Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Cough | -6.4 scores on a scale | Standard Error 1.3 |
| Durvalumab | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Dyspnea | 2.4 scores on a scale | Standard Error 1.24 |
| Durvalumab | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Chest pain | -1.0 scores on a scale | Standard Error 1.26 |
| Platinum-based SoC | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Cough | -7.9 scores on a scale | Standard Error 1.41 |
| Platinum-based SoC | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Dyspnea | 4.1 scores on a scale | Standard Error 1.32 |
| Platinum-based SoC | Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13) | Chest pain | -0.2 scores on a scale | Standard Error 1.37 |
Secondary
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months.
Time frame: Baseline and 12 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Global health status | -1.4 scores on a scale | Standard Error 1.23 |
| Durvalumab | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Fatigue | 2.2 scores on a scale | Standard Error 1.33 |
| Durvalumab | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Appetite loss | -0.2 scores on a scale | Standard Error 1.43 |
| Durvalumab | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Physical functioning | -3.9 scores on a scale | Standard Error 1.22 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Appetite loss | 9.8 scores on a scale | Standard Error 1.52 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Global health status | -7.3 scores on a scale | Standard Error 1.31 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Physical functioning | -6.0 scores on a scale | Standard Error 1.29 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Fatigue | 7.7 scores on a scale | Standard Error 1.42 |
Secondary
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months.
Time frame: Baseline and 12 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Cough | -6.6 scores on a scale | Standard Error 1.38 |
| Durvalumab | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Dyspnea | 2.9 scores on a scale | Standard Error 1.28 |
| Durvalumab | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Chest pain | -0.7 scores on a scale | Standard Error 1.3 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Cough | -8.6 scores on a scale | Standard Error 1.48 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Dyspnea | 3.9 scores on a scale | Standard Error 1.35 |
| Platinum-based SoC | Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Chest pain | -1.0 scores on a scale | Standard Error 1.4 |
Secondary
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)
The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months.
Time frame: Baseline and 12 months
Population: The FAS included all randomized participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durvalumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Global health status | -0.7 scores on a scale | Standard Error 1.19 |
| Durvalumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Physical functioning | -3.3 scores on a scale | Standard Error 1.23 |
| Durvalumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Fatigue | 1.4 scores on a scale | Standard Error 1.33 |
| Durvalumab | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Appetite loss | -1.1 scores on a scale | Standard Error 1.39 |
| Platinum-based SoC | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Appetite loss | 9.1 scores on a scale | Standard Error 1.5 |
| Platinum-based SoC | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Global health status | -7.4 scores on a scale | Standard Error 1.27 |
| Platinum-based SoC | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Fatigue | 7.2 scores on a scale | Standard Error 1.43 |
| Platinum-based SoC | Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30) | Physical functioning | -6.1 scores on a scale | Standard Error 1.3 |
Secondary
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set
DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set | 11.6 months |
| Platinum-based SoC | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set | 4.2 months |
Secondary
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set
DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set | 12.2 months |
| Platinum-based SoC | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set | 4.2 months |
Secondary
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set
DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set | 12.2 months |
| Platinum-based SoC | DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set | 4.2 months |
Secondary
Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment
DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment | 11.9 months |
| Platinum-based SoC | Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment | 4.2 months |
Secondary
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported.
Time frame: From Baseline and until follow-up period of 57 months
Population: The FAS included all randomized participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Restricted activity, Baseline | 267 number of participants |
| Durvalumab | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Restricted activity, Follow-up Month 57 | 0 number of participants |
| Platinum-based SoC | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Restricted activity, Follow-up Month 57 | 2 number of participants |
| Platinum-based SoC | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status | Restricted activity, Baseline | 255 number of participants |
Secondary
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set
ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported.
Time frame: From Baseline and until follow-up period of 57 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab | Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set | Restricted activity, Baseline | 221 number of participants |
| Durvalumab | Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set | Restricted activity, Follow-up Month 57 | 0 number of participants |
| Platinum-based SoC | Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set | Restricted activity, Follow-up Month 57 | 2 number of participants |
| Platinum-based SoC | Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set | Restricted activity, Baseline | 203 number of participants |
Secondary
Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment
ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs). Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.
Time frame: 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)
Population: The FAS included all randomized participants who had PD-L1 expression TC \>= 25% with the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment | 37.6 percentage of participants |
| Platinum-based SoC | Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment | 37.4 percentage of participants |
Secondary
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set
ORR (per RECIST 1.1 using Investigator assessments)was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.
Time frame: 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)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set | 38.5 percentage of participants |
| Platinum-based SoC | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set | 40.2 percentage of participants |
Secondary
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set
ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.
Time frame: 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)
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set | 42.1 percentage of participants |
| Platinum-based SoC | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set | 40.7 percentage of participants |
Secondary
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set
ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.
Time frame: 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)
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set | 44.0 percentage of participants |
| Platinum-based SoC | ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set | 43.7 percentage of participants |
Secondary
OS at 18 Months
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.
Time frame: From date of randomization till 18 months.
Population: The FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 18 Months | 42.5 percentage of participants |
| Platinum-based SoC | OS at 18 Months | 34.2 percentage of participants |
Secondary
OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.
Time frame: From date of randomization till 18 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set | 43.0 percentage of participants |
| Platinum-based SoC | OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set | 41.4 percentage of participants |
Secondary
OS at 18 Months in PD-L1 TC >= 50% Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.
Time frame: From date of randomization till 18 months
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 18 Months in PD-L1 TC >= 50% Analysis Set | 43.2 percentage of participants |
| Platinum-based SoC | OS at 18 Months in PD-L1 TC >= 50% Analysis Set | 34.9 percentage of participants |
Secondary
OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.
Time frame: From date of randomization till 18 months
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set | 44.3 percentage of participants |
| Platinum-based SoC | OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set | 42.2 percentage of participants |
Secondary
OS at 24 Months
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.
Time frame: From date of randomization till 24 months
Population: The FAS included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 24 Months | 34.6 percentage of participants |
| Platinum-based SoC | OS at 24 Months | 27.2 percentage of participants |
Secondary
OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.
Time frame: From date of randomization till 24 months
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set | 34.7 percentage of participants |
| Platinum-based SoC | OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set | 32.8 percentage of participants |
Secondary
OS at 24 Months in PD-L1 TC >= 50% Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.
Time frame: From date of randomization till 24 months
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 24 Months in PD-L1 TC >= 50% Analysis Set | 37.0 percentage of participants |
| Platinum-based SoC | OS at 24 Months in PD-L1 TC >= 50% Analysis Set | 27.0 percentage of participants |
Secondary
OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set
OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.
Time frame: From date of randomization till 24 months
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Durvalumab | OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set | 36.9 percentage of participants |
| Platinum-based SoC | OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set | 32.6 percentage of participants |
Secondary
OS in PD-L1 TC >= 50% Analysis Set
OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
Time frame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | OS in PD-L1 TC >= 50% Analysis Set | 14.6 months |
| Platinum-based SoC | OS in PD-L1 TC >= 50% Analysis Set | 11.8 months |
Secondary
OS in PD-L1 TC >= 50% LREM Analysis Set
OS is defined as the time from the date of randomization until death due to ay cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.
Time frame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | OS in PD-L1 TC >= 50% LREM Analysis Set | 14.9 months |
| Platinum-based SoC | OS in PD-L1 TC >= 50% LREM Analysis Set | 14.9 months |
Secondary
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set
Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time frame: Up to 24 weeks
Population: The ADA evaluable LREM analysis set included all participants in the safety analysis set who had a non-missing baseline ADA and at least 1 non-missing post-baseline ADA result, and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab | Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set | Treatment-emergent ADA positive | 1.0 percentage of participants |
| Durvalumab | Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set | Treatment-boosted ADA | 0.5 percentage of participants |
| Durvalumab | Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set | Persistently positive | 0 percentage of participants |
| Durvalumab | Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set | Transiently positive | 1.0 percentage of participants |
Secondary
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab
Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time frame: Up to 24 weeks
Population: The ADA evaluable analysis set included all participants in the safety analysis set who had a non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Durvalumab | Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab | Treatment-emergent ADA positive | 0.8 percentage of participants |
| Durvalumab | Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab | Treatment-boosted ADA | 0.4 percentage of participants |
| Durvalumab | Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab | Persistently positive | 0 percentage of participants |
| Durvalumab | Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab | Transiently positive | 0.8 percentage of participants |
Secondary
PFS2 in PD-L1 TC >= 25% LREM Analysis Set
PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS2 in PD-L1 TC >= 25% LREM Analysis Set | 11.8 months |
| Platinum-based SoC | PFS2 in PD-L1 TC >= 25% LREM Analysis Set | 10.9 months |
Secondary
PFS2 in PD-L1 TC >= 50% Analysis Set
PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS2 in PD-L1 TC >= 50% Analysis Set | 11.3 months |
| Platinum-based SoC | PFS2 in PD-L1 TC >= 50% Analysis Set | 8.8 months |
Secondary
PFS2 in PD-L1 TC >= 50% LREM Analysis Set
PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS2 in PD-L1 TC >= 50% LREM Analysis Set | 12.0 months |
| Platinum-based SoC | PFS2 in PD-L1 TC >= 50% LREM Analysis Set | 10.9 months |
Secondary
PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set
The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).
Time frame: 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)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set | 5.5 months |
| Platinum-based SoC | PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set | 5.6 months |
Secondary
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set
The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).
Time frame: 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)
Population: The PD-L1 TC \>= 50% analysis set included the subset of participants in the FAS whose PD-L1 expression status was PD-L1 TC \>= 50% as defined by the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set | 5.6 months |
| Platinum-based SoC | PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set | 4.5 months |
Secondary
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set
The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).
Time frame: 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)
Population: The PD-L1 TC \>= 50% LREM analysis set included participants with PD-L1 TC \>= 50% and identified by a prognostic model developed by AstraZeneca as having LREM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set | 5.7 months |
| Platinum-based SoC | PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set | 5.5 months |
Secondary
Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
The PFS (per RECIST 1.1) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). Progression of disease per RECIST 1.1, when either 1 of the criteria met: Target lesion (TL): at least a 20% increase in the sum of diameters of TLs, for reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Non-target lesion (NTL): Unequivocal progression of existing NTLs. It may be due to an important progression in 1 lesion only or in several lesions. In all cases the progression must be clinically significant for the physician to consider changing (or stopping) therapy. New lesions: the presence of 1 or more new lesions was assessed as progression.
Time frame: 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)
Population: The FAS included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 5.4 months |
| Platinum-based SoC | Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | 4.8 months |
Secondary
Time From Randomization to Second Progression (PFS2)
PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.
Time frame: 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)
Population: The FAS included all randomized participants who had PD-L1 expression TC \>= 25% with the VENTANA PD-L1 (SP263) assay.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Durvalumab | Time From Randomization to Second Progression (PFS2) | 11.3 months |
| Platinum-based SoC | Time From Randomization to Second Progression (PFS2) | 9.3 months |
Secondary
Time to Deterioration of EORTC QLQ-C30
Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration (a decrease in the function scales or the global health status/ health-related quality of life \[HRQoL\] from baseline of ≥10) that was confirmed at a subsequent visit or death in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.
Time frame: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 | Global health status | 7.3 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 | Physical functioning | 7.4 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 | Appetite loss | 9.2 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 | Fatigue | 4.9 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 | Fatigue | 1.8 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 | Global health status | 3.8 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 | Appetite loss | 3.6 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 | Physical functioning | 3.8 months |
Secondary
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.
Time frame: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Global health status | 7.4 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Physical functioning | 7.4 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Appetite loss | 9.3 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Fatigue | 5.5 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Fatigue | 1.8 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Global health status | 5.5 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Appetite loss | 3.7 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set | Physical functioning | 4.7 months |
Secondary
Time to Deterioration of EORTC QLQ-LC13
Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication.
Time frame: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Population: The FAS included all randomized participants. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 | Dyspnea | 2.8 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 | Chest pain | 9.0 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 | Cough | 7.5 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 | Dyspnea | 3.6 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 | Cough | 6.6 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 | Chest pain | 6.4 months |
Secondary
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication.
Time frame: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Population: The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM. Only data from the participants analyzed were reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Cough | 9.2 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Dyspnea | 3.6 months |
| Durvalumab | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Chest pain | 9.8 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Cough | 8.2 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Dyspnea | 3.6 months |
| Platinum-based SoC | Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set | Chest pain | 6.6 months |