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 were 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.

The PD-L1 (TC >=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by Ventana PD-L1 (SP263) assay (ie, >=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab monotherapy Vs SoC and durvalumab + tremelimumab Vs SoC reporting groups were analysed for primary outcome measure.

The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs SoC chemotherapy reporting groups were analysed for the primary outcome measure.

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 were 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.

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab monotherapy reporting groups were analysed for the secondary outcome measure.

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 were 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.

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane).

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 were 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.

The FAS included all randomized participants analyzed on an ITT basis.

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

The PD-L1 (TC >=25%) analysis set included subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by Ventana PD-L1 (SP263) assay (ie, >=25% TCs expressing PD-L1 on the membrane). Comparison of durvalumab + tremelimumab Vs durvalumab and durvalumab Vs SoC reporting groups were analysed for secondary outcome measure.

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane).

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

The FAS included all randomized participants analyzed on an ITT basis.

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TC expressing PD-L1 on the membrane).

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane).

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The FAS included all randomized participants analyzed on an ITT basis.

The DoR per RECIST 1.1 using BICR 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 (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie,>=25% TC expressing PD-L1 on the membrane). DoR is only analyzed for those participants with a response (including unconfirmed responses).

The DoR per RECIST 1.1 using BICR 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 disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane). DoR is only analyzed for those participants with a response (including unconfirmed responses).

The DoR per RECIST 1.1 using BICR 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 (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).

The FAS included all randomized participants analyzed on an ITT basis. DoR is only analyzed for those participants with a response (including unconfirmed responses).

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TC expressing PD-L1 on the membrane).

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane).

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.

The FAS included all randomized participants analyzed on an ITT basis.

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 and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TC expressing PD-L1 on the membrane).

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 and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.

The PD-L1 (TC >=1%) analysis set included the subset of participants in the FAS whose PD-L1 status is PD-L1 (TC >=1%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=1% TC expressing PD-L1 on the membrane).

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 and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.

The FAS included all randomized participants analyzed on an ITT basis.

Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of >=10.

The PD-L1 (TC >=25%) analysis set included the subset of participants in the FAS whose PD-L1 status was PD-L1 (TC >=25%) as defined by the Ventana PD-L1 (SP263) assay (ie, >=25% TC expressing PD-L1 on the membrane).

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

Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

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

The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the Cmax_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the Cmax_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the Ctrough_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were collected to determine the Ctrough_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.

The PK analysis set included all participants who received at least 1 dose of study treatment per the protocol for whom any post-dose data are available and who did not violate or deviate from the protocol in ways that would materially affect the PK analyses.

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. 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 one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing durvalumab baseline ADA and at least one non-missing post-baseline durvalumab ADA result.

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. 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 one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

Safety analysis set included all participants who received at least 1 dose of study treatment. ADA evaluable population included participants who have non-missing baseline tremelimumab ADA and at least one non-missing post-baseline tremelimumab ADA result.