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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Non Small Cell Lung Carcinoma NSCLC
• Intervention / Treatment: Drug: Paclitaxel + carboplatin; Drug: Gemcitabine + cisplatin; Drug: Gemcitabine + carboplatin; Drug: Pemetrexed + cisplatin; Drug: Pemetrexed + carboplatin; Drug: Durvalumab (MEDI4736)

Detailed Description

Patients with stage IV NSCLC will be randomized in a 1:1 ratio to 2 treatment arms (durvalumab or SOC therapy). The dual primary objectives of this study are to assess the efficacy of durvalumab versus SoC in terms of OS (Overall Survival) in all randomized patients and in patients who are at low risk of EM (early mortality)

• Study Type: Interventional
• Enrollment (Actual): 669
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Gosford, Australia, 2250
    • Research Site
  • Kogarah, Australia, 2217
    • Research Site
  • St Leonards, Australia, 2065
    • Research Site
• China
  • Beijing, China, 100142
    • Research Site
  • Beijing, China, 100853
    • Research Site
  • Beijing, China, 100032
    • Research Site
  • Bengbu, China, 233060
    • Research Site
  • Changchun, China, 130000
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China, 400030
    • Research Site
  • Guangzhou, China, 510080
    • Research Site
  • Guangzhou, China, 510095
    • Research Site
  • Haikou, China, 570311
    • Research Site
  • Hangzhou, China, 310006
    • Research Site
  • Hangzhou, China, 310022
    • Research Site
  • Hangzhou, China, 310003
    • Research Site
  • Hangzhou, China, 310009
    • Research Site
  • Jinan, China, 250031
    • Research Site
  • Linhai, China, 317000
    • Research Site
  • Nanchang, China, 330006
    • Research Site
  • Nanjing, China, 210009
    • Research Site
  • Ningbo, China, 315010
    • Research Site
  • Shanghai, China, 200030
    • Research Site
  • Shenyang, China, 110042
    • Research Site
  • Shijiazhuang, China, 050020
    • Research Site
  • Urumqi, China, 830000
    • Research Site
  • Urumqi, China, 830054
    • Research Site
  • Wanzhou, China, 404000
    • Research Site
  • Wenzhou, China, CN-325000
    • Research Site
  • Wuhan, China, 430022
    • Research Site
  • Wuhan, China, 430030
    • Research Site
  • Wuhan, China, 430010
    • Research Site
  • Xi'an, China, 710061
    • Research Site
  • Xi'an, China, 710038
    • Research Site
  • Zhengzhou, China, 450008
    • Research Site
  • Zhuhai, China, 519099
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Budapest, Hungary, 1121
    • Research Site
  • Budapest, Hungary, 1122
    • Research Site
  • Deszk, Hungary, 6772
    • Research Site
  • Farkasgyepü, Hungary, 8582
    • Research Site
  • Gyöngyös - Mátraháza, Hungary, 3200
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
  • Törökbálint, Hungary, 2045
    • Research Site
• Korea, Republic of
  • Changwon-si, Korea, Republic of, 51353
    • Research Site
  • Cheongju-si, Korea, Republic of, 28644
    • Research Site
  • Daegu, Korea, Republic of, 42415
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Jinju-si, Korea, Republic of, 660-702
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
• Netherlands
  • Almelo, Netherlands, 7600SZ
    • Research Site
• Poland
  • Bialystok, Poland, 15-027
    • Research Site
  • Grudziądz, Poland, 86-300
    • Research Site
  • Koszalin, Poland, 75-581
    • Research Site
  • Lublin, Poland, 20-090
    • Research Site
  • Mrozy, Poland, 05-320
    • Research Site
  • Warszawa, Poland, 02-781
    • Research Site
  • Wroclaw, Poland, 53-413
    • Research Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Research Site
  • Moscow, Russian Federation, 115478
    • Research Site
  • Novosibirsk, Russian Federation, 630108
    • Research Site
  • Omsk, Russian Federation, 644013
    • Research Site
  • Rostov-on-Don, Russian Federation, 344037
    • Research Site
  • Saint Petersburg, Russian Federation, 197342
    • Research Site
  • Saint Petersburg, Russian Federation, 197758
    • Research Site
  • Saint-Petersburg, Russian Federation, 194291
    • Research Site
  • Saint-Petersburg, Russian Federation, 197183
    • Research Site
  • Sankt-Peterburg, Russian Federation, 196603
    • Research Site
  • St. Petersburg, Russian Federation, 197758
    • Research Site
  • Volgograd, Russian Federation, 400138
    • Research Site
• Taiwan
  • Taichung, Taiwan, 40705
    • Research Site
  • Taichung City, Taiwan, 402
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Bangkok, Thailand, 10700
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
  • Songkla, Thailand, 90110
    • Research Site
• Turkey
  • Ankara, Turkey, 06490
    • Research Site
  • Istanbul, Turkey, 34030
    • Research Site
  • Istanbul, Turkey, 34854
    • Research Site
  • Malatya, Turkey, 44100
    • Research Site
  • Pamukkale, Turkey, 20070
    • Research Site
• United States
  • California
    • Anaheim, California, United States, 92801
      • Research Site
• Vietnam
  • Can Tho, Vietnam, 900000
    • Research Site
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Research Site
  • Ho Chi Minh, Vietnam, 70000
    • Research Site
  • Ho Chi Minh, Vietnam, 10000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 128 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: Durvalumab; Anti-PD-L1 monoclonal Antibody monotherapy	Drug: Durvalumab (MEDI4736); Anti-PD-L1 monoclonal Antibody monotherapy
Active Comparator: Arm 2: Standard of Care; Standard of Care Platinum-Based chemotherapy	Drug: Paclitaxel + carboplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Gemcitabine + cisplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Gemcitabine + carboplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Pemetrexed + cisplatin; Chemotherapy Agent; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Pemetrexed + carboplatin; Chemotherapy Agent; Other Names: Platinum based Standard of Care Chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.	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 in Participants With LREM	OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.	From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS in PD-L1 TC >= 50% Analysis Set	OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.	From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
OS in PD-L1 TC >= 50% LREM Analysis Set	OS is defined as the time from the date of randomization until death due to ay cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive.	From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	The PFS (per RECIST 1.1) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). Progression of disease per RECIST 1.1, when either 1 of the criteria met: Target lesion (TL): at least a 20% increase in the sum of diameters of TLs, for reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Non-target lesion (NTL): Unequivocal progression of existing NTLs. It may be due to an important progression in 1 lesion only or in several lesions. In all cases the progression must be clinically significant for the physician to consider changing (or stopping) therapy. New lesions: the presence of 1 or more new lesions was assessed as progression.	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)
PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set	The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).	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)
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set	The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).	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)
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set	The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1).	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)
Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment	ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs). Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set	ORR (per RECIST 1.1 using Investigator assessments)was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set	ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set	ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met.	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)
Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment	DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set	DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set	DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.	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 as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set	DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique.	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)
Alive and Progression-Free at 12 Months (APF12)	The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.	From date of randomization until 12 months
APF12 in PD-L1 TC >= 25% LREM Analysis Set	The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.	From date of randomization until 12 months
APF12 in PD-L1 TC >= 50% Analysis Set	The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.	From date of randomization until 12 months
APF12 in PD-L1 TC >= 50% LREM Analysis Set	The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis.	From date of randomization until 12 months
Time From Randomization to Second Progression (PFS2)	PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.	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 in PD-L1 TC >= 25% LREM Analysis Set	PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.	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 in PD-L1 TC >= 50% Analysis Set	PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.	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 in PD-L1 TC >= 50% LREM Analysis Set	PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique.	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)
OS at 18 Months	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.	From date of randomization till 18 months.
OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.	From date of randomization till 18 months
OS at 18 Months in PD-L1 TC >= 50% Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.	From date of randomization till 18 months
OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months.	From date of randomization till 18 months
OS at 24 Months	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.	From date of randomization till 24 months
OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.	From date of randomization till 24 months
OS at 24 Months in PD-L1 TC >= 50% Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.	From date of randomization till 24 months
OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set	OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months.	From date of randomization till 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)	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.	Baseline and 12 months
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set	The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months.	Baseline and 12 months
Time to Deterioration of EORTC QLQ-C30	Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration (a decrease in the function scales or the global health status/ health-related quality of life [HRQoL] from baseline of ≥10) that was confirmed at a subsequent visit or death in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.	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 Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set	Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual.	From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)	The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months.	Baseline and 12 months
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set	The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months.	Baseline and 12 months
Time to Deterioration of EORTC QLQ-LC13	Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication.	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 Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set	Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication.	From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status	ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported.	From Baseline and until follow-up period of 57 months
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set	ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported.	From Baseline and until follow-up period of 57 months
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab	Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.	Up to 24 weeks
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set	Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.	Up to 24 weeks

Other Outcome Measures

Outcome Measure	Time Frame
The Incidence of Treatment-Emergent Adverse Events assessed by Common Terminology Criteria for Adverse Event (CTCAE) v4.03 for subjects receiving Durvalumab therapy or SoC	4 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Parker Suzanne, AstraZeneca RDM, South San Francisco, USA

Publications and helpful links

Helpful Links

• CSR Synopsis
• CSP
• SAP

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2017
• Primary Completion (Actual): October 27, 2022
• Study Completion (Estimated): June 4, 2026

Study Registration Dates

• First Submitted: December 15, 2016
• First Submitted That Met QC Criteria: December 22, 2016
• First Posted (Estimated): December 28, 2016

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; PD-L1; Durvalumab (MEDI4736); OS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Durvalumab; Pemetrexed; Gemcitabine
• Other Study ID Numbers: D419AC00002; 2018-001375-21 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No