Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)

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)

• Durvalumab (MEDI4736) (Drug): Anti-PD-L1 monoclonal Antibody monotherapy
• Paclitaxel + carboplatin (Drug), also known as Platinum based Standard of Care Chemotherapy: Chemotherapy Agents
• Gemcitabine + cisplatin (Drug), also known as Platinum based Standard of Care Chemotherapy: Chemotherapy Agents
• Gemcitabine + carboplatin (Drug), also known as Platinum based Standard of Care Chemotherapy: Chemotherapy Agents
• Pemetrexed + cisplatin (Drug), also known as Platinum based Standard of Care Chemotherapy: Chemotherapy Agent
• Pemetrexed + carboplatin (Drug), also known as Platinum based Standard of Care Chemotherapy: Chemotherapy Agent

Primary outcomes

• 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 outcomes

• 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.
• 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% 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.

Sex: All, ages: 18 Years to 130 Years

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\]

Participant flow

Outcome results

• Overall Survival (OS) (Primary), Median, months: Durvalumab 14.6 (12.2 to 16.9); Platinum-based SoC 12.8 (10.1 to 14.7) (p 0.037)
• OS in Participants With LREM (Primary), Median, months: Durvalumab 14.6 (12.6 to 17.2); Platinum-based SoC 15.0 (13.1 to 16.8) (p 0.628)
• OS in PD-L1 TC >= 50% Analysis Set (Secondary), Median, months: Durvalumab 14.6 (12.0 to 17.7); Platinum-based SoC 11.8 (9.8 to 14.7)
• OS in PD-L1 TC >= 50% LREM Analysis Set (Secondary), Median, months: Durvalumab 14.9 (12.6 to 19.0); Platinum-based SoC 14.9 (11.8 to 17.7)
• Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) (Secondary), Median, months: Durvalumab 5.4 (4.2 to 5.7); Platinum-based SoC 4.8 (4.3 to 5.6)
• PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set (Secondary), Median, months: Durvalumab 5.5 (4.4 to 6.4); Platinum-based SoC 5.6 (4.8 to 5.9)
• PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set (Secondary), Median, months: Durvalumab 5.6 (4.7 to 6.5); Platinum-based SoC 4.5 (4.2 to 5.6)
• PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set (Secondary), Median, months: Durvalumab 5.7 (5.3 to 7.0); Platinum-based SoC 5.5 (4.2 to 5.7)
• Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment (Secondary), Number, percentage of participants: Durvalumab 37.6 (0.324 to 0.430); Platinum-based SoC 37.4 (0.322 to 0.429)
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set (Secondary), Number, percentage of participants: Durvalumab 38.5 (0.327 to 0.445); Platinum-based SoC 40.2 (0.343 to 0.463)
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set (Secondary), Number, percentage of participants: Durvalumab 42.1 (0.359 to 0.485); Platinum-based SoC 40.7 (0.345 to 0.471)
• ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set (Secondary), Number, percentage of participants: Durvalumab 44.0 (0.371 to 0.510); Platinum-based SoC 43.7 (0.367 to 0.509)
• Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment (Secondary), Median, months: Durvalumab 11.9 (9.7 to 18.7); Platinum-based SoC 4.2 (3.3 to 4.6)
• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set (Secondary), Median, months: Durvalumab 11.6 (8.2 to 15.7); Platinum-based SoC 4.2 (4.0 to 5.4)
• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set (Secondary), Median, months: Durvalumab 12.2 (8.3 to 21.2); Platinum-based SoC 4.2 (3.0 to 4.6)
• DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set (Secondary), Median, months: Durvalumab 12.2 (8.2 to 19.7); Platinum-based SoC 4.2 (3.9 to 5.4)
• Alive and Progression-Free at 12 Months (APF12) (Secondary), Number, percentage of participants: Durvalumab 25.5 (20.8 to 30.4); Platinum-based SoC 13.3 (9.6 to 17.5)
• APF12 in PD-L1 TC >= 25% LREM Analysis Set (Secondary), Number, percentage of participants: Durvalumab 24.1 (19.1 to 29.5); Platinum-based SoC 16.4 (11.9 to 21.5)
• APF12 in PD-L1 TC >= 50% Analysis Set (Secondary), Number, percentage of participants: Durvalumab 26.1 (20.7 to 31.9); Platinum-based SoC 11.7 (7.7 to 16.5)
• APF12 in PD-L1 TC >= 50% LREM Analysis Set (Secondary), Number, percentage of participants: Durvalumab 26.5 (20.5 to 32.8); Platinum-based SoC 14.5 (9.6 to 20.4)
• 24 more outcome measures not shown.

Adverse events

Time frame: From first administration of study treatment up to 90 days after the last dose of durvalumab or 30 days after last dose of platinum based SoC or date of initiation of the first subsequent therapy, whichever occurs first, for approximately 69 months.

Serious adverse events by term

105 more terms not shown.

Other adverse events by term

• Study Protocol (PDF, 2021-06-18)
• Statistical Analysis Plan (PDF, 2021-06-11)

NIH grants: 2018