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Tyrosine

MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.

Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.

MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.

MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

MEDI4736 (durvalumab) treatment by intravenous infusion

MEDI4736 (durvalumab)

Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.

Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.

Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration

Erlotinib

MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion

MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)

tremelimumab (anti-CTLA4) treatment by intravenous infusion

tremelimumab (anti-CTLA4)

Paul Stockman, MBChB, PhD

This study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the treatment of male and female patients with locally advanced or metastatic NSCLC (Stage IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1 platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements are not eligible for the study (prospective testing is not planned within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor (erlotinib \[TARCEVA®\]), gemcitabine or vinorelbine (NAVELBINE®)

The study has an umbrella design with 2 sub-studies: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 (durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of Care. The two substudies may have different durations of recruitment periods due to differences in patient population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occurring at different time points.

A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer

A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).

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

The OS was defined as the time from the date of randomization until death due to any cause.

The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to response evaluation criteria in solid tumours (RECIST) version 1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion

The OS12 was defined as the percentage of participants who were alive at 12 months after randomisation per Kaplan-Meier estimate of OS at 12 months.

The PFS 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 withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion

The ORR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) among ITT participants who had measurable disease at baseline. CR was defined as disappearance of all target lesions (any pathological lymph nodes selected as target lesions 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 target lesions (taking as reference the baseline sum of diameters as long as criteria for PD are not met). The ORR was measured using Investigator assessments according to RECIST v1.1.

The DoR 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. The DoR was determined by Investigator assessments according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion

The APF6 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 6 months after randomization per Kaplan-Meier estimate of PFS at 6 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion

The PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the PFS endpoint or death and determined by local standard clinical practice and have included any of the following: objective radiological, symptomatic progression, or death. PFS2 was reported for sub-study B only.

AstraZeneca

Sub-study A and B: Safety analysis set included all participants who received at least 1 dose of randomized treatment. All-cause mortality is defined as death due to any cause (including disease progression) for the entire duration of the study.

Participants received durvalumab 10 mg/kg IV infusion Q2W for 12 months (up to 26 doses).

Sub-study A: Durvalumab

Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m\^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m\^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.

Sub-study A: SoC

Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion Q4W for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).

Sub-study B: Durvalumab+Tremelimumab

Sub-study B: SoC

Sub-study B: Durvalumab

Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by Q12W for 24 weeks (up to 9 doses).

Sub-study B: Tremelimumab

Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/m\^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m\^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until PD, initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Sub-study A and B: Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Medical Science Director

For sub-study A: durvalumab monotherapy treatment arm was compared with SoC.

For sub-study B: durvalumab plus tremelimumab treatment arm was compared with SoC.

Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.

Overall Survival (OS)

Progression-Free Survival (PFS)

As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.

As part of the contribution of components analysis for sub-study B, durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.

FAS included all randomized participants analyzed on an ITT basis.

OS, Contribution of the Components Analysis of Sub-study B

Percentage of Participants Alive at 12 Months (OS12)

PFS, Contribution of the Components Analysis of Sub-study B

For sub-study B: durvalumab plus tremelimumab treatment arm was compared with durvalumab monotherapy.

For sub-study B: durvalumab plus tremelimumab treatment arm was compared with tremelimumab monotherapy.

Sub-study A and B: FAS included all randomized participants with measureable disease at baseline analyzed on an ITT basis.

Objective Response Rate (ORR)

Sub-study A and B: FAS included all randomized participants with measureable disease at baseline analyzed on an ITT basis. Only participants with objective response were analyzed.

Duration of Response (DoR)

Percentage of Participants Alive and Progression Free at 6 Months (APF6)

Percentage of Participants Alive and Progression Free at 12 Months (APF12)

Time From Randomisation to Second Progression (PFS2) of Sub-study B

Participants received durvalumab (MEDI4736) 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (Q2W) for 12 months (up to 26 doses).

Participants received either erlotinib 150 mg tablet orally once daily; gemcitabine 1000 mg/meter square (m\^2) IV infusion on Days 1, 8, and 15 of a 28-day cycle; or vinorelbine 30 mg/m\^2 IV infusion on Days 1, 8, 15, and 22 of a 28-day cycle until progression of disease (PD), initiation of alternative anti-cancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue treatment criterion occurred.

Sub-study A: Standard of Care (SoC)

Participants received durvalumab 20 mg/kg plus tremelimumab 1 mg/kg IV infusion every 4 weeks (Q4W) for 12 weeks (4 doses) followed by durvalumab alone 10 mg/kg IV infusion Q2W for 34 weeks starting at Week 16 (up to 18 additional doses).

Participants received tremelimumab 10 mg/kg IV infusion Q4W for 24 weeks followed by every 12 weeks (Q12W) for 24 weeks (up to 9 doses).

Overall Study

Micronutrients

Hematinics

Vitamins

Paclitaxel

Carboplatin

Pemetrexed

Albumin-Bound Paclitaxel

Cisplatin

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

MEDI4736 (Durvalumab)

MEDI4736 (Durvalumab)+Tremelimumab

Paclitaxel + Carboplatin

Gemcitabine + Cisplatin

Gemcitabine + Carboplatin

Pemetrexed + Cisplatin

Pemetrexed + Carboplatin

Stuart McIntosh, MD

Naiyer Rizvi, MD

This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy 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 locally advanced or metastatic NSCLC

Patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.

Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)

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

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.

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 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 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 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 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 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 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 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 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.

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.

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 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.

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.

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.

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.

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.

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. All-cause mortality was determined for participants in FAS.

Participants received durvalumab 20 mg/kg IV infusion Q4W until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.

Durvalumab Monotherapy

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 on durvalumab 20 mg/kg Q4W, starting on Week 16 until worsening of the disease under investigation, unless specific treatment discontinuation criteria were met.

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 worsening of disease under investigation, unless 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 tumors 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 tumors only).
4. Pemetrexed 500 mg/m\^2 and cisplatin 75 mg/m\^2 (For non-squamous tumors only; pemetrexed maintenance dose was permitted).
5. Pemetrexed 500 mg/m\^2 and carboplatin AUC 5 or 6 mg\*min/mL (For non-squamous tumors only; pemetrexed maintenance dose was permitted).

SoC Chemotherapy

Age, Continuous

Ethnicity (NIH/OMB)

Full analysis set (FAS) included all randomized participants analyzed on an intent-to-treat (ITT) basis.

Global Clinical Lead

Durvalumab Monotherapy Vs SoC Chemotherapy

Durvalumab + Tremelimumab Vs SoC Chemotherapy

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.

Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy

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.

Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy

Durvalumab + Tremelimumab Vs Durvalumab Monotherapy

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.

OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy

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).

OS; PD-L1 (TC >=1%) Analysis Set Population

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

OS; FAS Population

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.

PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy

PFS; PD-L1 (TC >=1%) Analysis Set Population

PFS; FAS Population

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).

Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population

ORR; PD-L1 (TC >=1%) Analysis Set Population

ORR; FAS Population

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).

Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population

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).

DoR; PD-L1 (TC >=1%) Analysis Set Population

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer	NCT02352948	Non - Small Cel...	MEDI4736 (durva... Vinorelbine Gemcitabine Erlotinib MEDI4736 (durva... tremelimumab (a...	18 Years - 130 Years	AstraZeneca
Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)	NCT02453282	Non-Small-Cell ...	MEDI4736 (Durva... MEDI4736 (Durva... Paclitaxel + Ca... Gemcitabine + C... Gemcitabine + C... Pemetrexed + Ci... Pemetrexed + Ca... Tremelimumab	18 Years - 130 Years	AstraZeneca
An Open-Label, Multi-Centre, Study to Assess the Safety of Fixed-Dose Durvalumab + Tremelimumab Combination Therapy or Durvalumab Monotherapy in Advanced Solid Malignancies.	NCT03084471	Advanced Solid ...	MEDI4736 (Durva... MEDI4736 (Durva...	18 Years - 130 Years	AstraZeneca
Study of Mogamulizumab + MEDI4736 (Durvalumab) and Mogamulizumab + Tremelimumab in Subjects w/ Advanced Solid Tumors	NCT02301130	Advanced Solid ...	mogamulizumab MEDI4736 (Durva... tremelimumab	18 Years -	Kyowa Kirin Co., Ltd.

Spots Global Cancer Trial Database for medi4736 (durvalumab)