Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

All Drugs and Chemicals

Antineoplastic Agents

Micronutrients

Hematinics

Vitamins

Antibodies

Antibodies, Monoclonal

Gemcitabine

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Durvalumab

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antineoplastic Agents, Immunological

Folinic Acid

Folate

Vitamin B9

Anti-PD-L1 monoclonal Antibody monotherapy

Standard of Care Platinum-Based chemotherapy

Durvalumab (MEDI4736)

Paclitaxel + carboplatin

Gemcitabine + cisplatin

Gemcitabine + carboplatin

Pemetrexed + cisplatin

Pemetrexed + carboplatin

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)

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)

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

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

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 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.

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.

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).

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 (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 (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.

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.

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.

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 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 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.

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.

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 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 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.

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 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.

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.

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.

AstraZeneca

The Safety analysis set included all participants who received at least 1 dose of study treatment. All-cause mortality was in FAS analysis set.

Participants received durvalumab 20 mg/kg via IV infusion Q4W until documented PD or unacceptable toxicity or until specific treatment discontinuation criteria were met.

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).

Platinum-based SoC

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

The Full analysis set (FAS) included all randomized participants.

Global Clinical Lead

The FAS included all randomized participants.

Overall Survival (OS)

The PD-L1 TC \>= 25% LREM analysis set included participants identified by a prognostic model developed by AstraZeneca as having LREM.

OS in Participants With LREM

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.

OS in PD-L1 TC >= 50% Analysis Set

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 o 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).

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.

OS in PD-L1 TC >= 50% LREM Analysis Set

Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set

PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set

PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set

The FAS included all randomized participants who had PD-L1 expression TC \>= 25% with the VENTANA PD-L1 (SP263) assay.

Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set

Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set

Alive and Progression-Free at 12 Months (APF12)

APF12 in PD-L1 TC >= 25% LREM Analysis Set

APF12 in PD-L1 TC >= 50% Analysis Set

APF12 in PD-L1 TC >= 50% LREM Analysis Set

Time From Randomization to Second Progression (PFS2)

PFS2 in PD-L1 TC >= 25% LREM Analysis Set

PFS2 in PD-L1 TC >= 50% Analysis Set

PFS2 in PD-L1 TC >= 50% LREM Analysis Set

OS at 18 Months

OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set

OS at 18 Months in PD-L1 TC >= 50% Analysis Set

OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set

OS at 24 Months

OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set

OS at 24 Months in PD-L1 TC >= 50% Analysis Set

OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set

Global health status

Physical functioning

Fatigue

Appetite loss

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 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.

Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set

The FAS included all randomized participants. Only data from the participants analyzed were reported.

Time to Deterioration of EORTC QLQ-C30

Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set

Cough

Dyspnea

Chest pain

Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)

Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set

Time to Deterioration of EORTC QLQ-LC13

Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set

Restricted activity, Baseline

Restricted activity, Follow-up Month 57

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.
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).

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set

Treatment-emergent ADA positive

Treatment-boosted ADA

Persistently positive

Transiently positive

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.

Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab

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.

Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set

Participants received durvalumab 20 milligram (mg)/kilogram (kg) via intravenous (IV) infusion every 4 weeks (Q4W) until documented disease progression (PD) or unacceptable toxicity or until specific treatment discontinuation criteria were met.

Participants received 1 of the following IV infusion treatment combination platinum-based standard of care (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/ square meter (m\^2) and carboplatin area under the plasma concentration curve (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).

Overall Study

Tremelimumab

Durvalumab (PD-L1 monoclonal antibody) + Tremelimumab (monoclonal antibody directed against CTLA-4)

Durvalumab +Tremelimumab

Gilberto de Castro

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.

Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.

Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)

A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC).

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

The OS was defined as the time from the date of randomization until death due to any cause (ie, 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. Median OS was calculated using the Kaplan-Meier technique.

OS was defined as time from date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at time of analysis was censored based on last recorded date on which participant was known to be alive.

bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb and bTMB \<20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥16 mut/Mb, ≥12 mut/Mb and \<20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available.

tTMB analysis sets are defined same as the bTMB analysis sets.

The OS was defined as time from date of randomization until death due to any cause (ie, 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 last recorded date on which participant was known to be alive.

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 \[RECIST 1.1\] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).

PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: FAS included all randomized participants prior to end of global recruitment.

China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included subset of participants in FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD.

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD.

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay.

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The APF12 was defined as the percentage of participants who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).

bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).

PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, \<1% PD-L1-membrane expression in tumoral tissue).

Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

Blood samples were collected to determine the serum concentration of durvalumab.

Blood samples were collected to determine the serum concentration of tremelimumab.

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to \>=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Global Cohort: The safety analysis set included all participants recruited prior to end of the global recruitment who received at least 1 dose of study treatment.

China Cohort: The China safety analysis set included all participants recruited in the China cohort who received at least 1 dose of study treatment.

All-Cause Mortality: Data from participants included in Global and China FAS was summarized separately. 30 participants in China cohort were also included in Global cohort.

Participants received durvalumab 20 mg/kg and tremelimumab 1 mg/kg IV infusion Q4W in combination for up to 4 doses/cycles. Participants then continued to receive durvalumab 20 mg/kg Q4W, starting on Week 16 until objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or specific treatment discontinuation criteria were met.

Global: Durvalumab + Tremelimumab

Participants received 1 of the following IV infusion treatment combinations on Day 1 of each 21-day cycle for 4 to 6 cycles or until objective PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or specific treatment discontinuation criteria were met.

1. Paclitaxel 200 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL.
2. Gemcitabine 1000 or 1250 mg/m\^2 and cisplatin 75 or 80 mg/m\^2. Additional dose of gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous participants only).
3. Gemcitabine 1000 or 1250 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL. Additional dose of gemcitabine 1000 or 1250 mg/m\^2 on Day 8 of each cycle (For squamous participants only).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous participants only; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous participants only; pemetrexed maintenance dose was permitted).

Global: SoC Chemotherapy

China: Durvalumab + Tremelimumab

China: SoC Chemotherapy

All Participants: Durvalumab + Tremelimumab

All Participants: SoC Chemotherapy

All participants

Global cohort

China cohort

Baseline data is presented for all participants, as well as separately for the Global and China cohorts.

Age, Customized

Global Cohort: The full analysis set (FAS) included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.

China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.

Participants included in both cohorts are not double-counted for the baseline characteristics analysis represented by 'All participants'.

Analysis of the China cohort was performed to evaluate the consistency of efficacy and safety in Chinese participants with the global cohort in order to meet China health regulatory requirements and was not powered for a formal assessment of statistical significance.

Global: Durvalumab + Tremelimumab versus (Vs) Global: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

The bTMB ≥20 mut/Mb analysis set included the subset of participants in the FAS whose blood TMB status was ≥20 mut/Mb at baseline as defined by the GuardantOMNI CDx assay. Only participants randomized in Global cohort were analyzed as bTMB and tissue tumor mutational burden (tTMB) testing was not performed in China cohort.

Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set

China: Durvalumab + Tremelimumab Vs China: SoC Chemotherapy

A HR \<1 favors Durvalumab + Tremelimumab combination therapy to be associated with a longer OS than SoC.

The China PD-L1-negative population analysis set included the subset of participants in the China FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 assay (ie, \<1% PD-L1-membrane expression in tumoral tissue). Only participants randomized in China cohort were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)	NCT03003962	Non Small Cell ...	Durvalumab (MED... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca
Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)	NCT02542293	Non Small Cell ...	Durvalumab +Tre... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca
Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)	NCT02542293	Non Small Cell ...	Durvalumab +Tre... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca
Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)	NCT03003962	Non Small Cell ...	Durvalumab (MED... Paclitaxel + ca... Gemcitabine + c... Gemcitabine + c... Pemetrexed + ci... Pemetrexed + ca...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for non small cell lung carcinoma nsclc