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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03003962




Registration number
NCT03003962
Ethics application status
Date submitted
15/12/2016
Date registered
28/12/2016
Date last updated
19/09/2024

Titles & IDs
Public title
Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)
Scientific title
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
Secondary ID [1] 0 0
2018-001375-21
Secondary ID [2] 0 0
D419AC00002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Carcinoma NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Durvalumab (MEDI4736)
Treatment: Drugs - Paclitaxel + carboplatin
Treatment: Drugs - Gemcitabine + cisplatin
Treatment: Drugs - Gemcitabine + carboplatin
Treatment: Drugs - Pemetrexed + cisplatin
Treatment: Drugs - Pemetrexed + carboplatin

Experimental: Arm 1: Durvalumab - Anti-PD-L1 monoclonal Antibody monotherapy

Active comparator: Arm 2: Standard of Care - Standard of Care Platinum-Based chemotherapy


Treatment: Drugs: Durvalumab (MEDI4736)
Anti-PD-L1 monoclonal Antibody monotherapy

Treatment: Drugs: Paclitaxel + carboplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + cisplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + carboplatin
Chemotherapy Agents

Treatment: Drugs: Pemetrexed + cisplatin
Chemotherapy Agent

Treatment: Drugs: Pemetrexed + carboplatin
Chemotherapy Agent
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
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]
Primary outcome [2] 0 0
OS in Participants With LREM
Timepoint [2] 0 0
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 [1] 0 0
OS in PD-L1 TC >= 50% Analysis Set
Timepoint [1] 0 0
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 [2] 0 0
OS in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [2] 0 0
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 [3] 0 0
Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set
Timepoint [5] 0 0
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)
Secondary outcome [6] 0 0
PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [6] 0 0
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)
Secondary outcome [7] 0 0
Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment
Timepoint [7] 0 0
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)
Secondary outcome [8] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [8] 0 0
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)
Secondary outcome [9] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment
Timepoint [11] 0 0
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)
Secondary outcome [12] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set
Timepoint [14] 0 0
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)
Secondary outcome [15] 0 0
Alive and Progression-Free at 12 Months (APF12)
Timepoint [15] 0 0
From date of randomization until 12 months
Secondary outcome [16] 0 0
APF12 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [16] 0 0
From date of randomization until 12 months
Secondary outcome [17] 0 0
APF12 in PD-L1 TC >= 50% Analysis Set
Timepoint [17] 0 0
From date of randomization until 12 months
Secondary outcome [18] 0 0
APF12 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [18] 0 0
From date of randomization until 12 months
Secondary outcome [19] 0 0
Time From Randomization to Second Progression (PFS2)
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
PFS2 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
PFS2 in PD-L1 TC >= 50% Analysis Set
Timepoint [21] 0 0
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)
Secondary outcome [22] 0 0
PFS2 in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [22] 0 0
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)
Secondary outcome [23] 0 0
OS at 18 Months
Timepoint [23] 0 0
From date of randomization till 18 months.
Secondary outcome [24] 0 0
OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set
Timepoint [24] 0 0
From date of randomization till 18 months
Secondary outcome [25] 0 0
OS at 18 Months in PD-L1 TC >= 50% Analysis Set
Timepoint [25] 0 0
From date of randomization till 18 months
Secondary outcome [26] 0 0
OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [26] 0 0
From date of randomization till 18 months
Secondary outcome [27] 0 0
OS at 24 Months
Timepoint [27] 0 0
From date of randomization till 24 months
Secondary outcome [28] 0 0
OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set
Timepoint [28] 0 0
From date of randomization till 24 months
Secondary outcome [29] 0 0
OS at 24 Months in PD-L1 TC >= 50% Analysis Set
Timepoint [29] 0 0
From date of randomization till 24 months
Secondary outcome [30] 0 0
OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set
Timepoint [30] 0 0
From date of randomization till 24 months
Secondary outcome [31] 0 0
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)
Timepoint [31] 0 0
Baseline and 12 months
Secondary outcome [32] 0 0
Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [32] 0 0
Baseline and 12 months
Secondary outcome [33] 0 0
Time to Deterioration of EORTC QLQ-C30
Timepoint [33] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [34] 0 0
Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [34] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [35] 0 0
Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)
Timepoint [35] 0 0
Baseline and 12 months
Secondary outcome [36] 0 0
Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [36] 0 0
Baseline and 12 months
Secondary outcome [37] 0 0
Time to Deterioration of EORTC QLQ-LC13
Timepoint [37] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [38] 0 0
Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
Timepoint [38] 0 0
From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcome [39] 0 0
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [39] 0 0
From Baseline and until follow-up period of 57 months
Secondary outcome [40] 0 0
Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set
Timepoint [40] 0 0
From Baseline and until follow-up period of 57 months
Secondary outcome [41] 0 0
Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab
Timepoint [41] 0 0
Up to 24 weeks
Secondary outcome [42] 0 0
Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set
Timepoint [42] 0 0
Up to 24 weeks

Eligibility
Key inclusion criteria
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
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
Accrual to date
Final
669
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Gosford
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
China
State/province [2] 0 0
Beijing
Country [3] 0 0
China
State/province [3] 0 0
Bengbu
Country [4] 0 0
China
State/province [4] 0 0
Changchun
Country [5] 0 0
China
State/province [5] 0 0
Changsha
Country [6] 0 0
China
State/province [6] 0 0
Chengdu
Country [7] 0 0
China
State/province [7] 0 0
Chongqing
Country [8] 0 0
China
State/province [8] 0 0
Guangzhou
Country [9] 0 0
China
State/province [9] 0 0
Haikou
Country [10] 0 0
China
State/province [10] 0 0
Hangzhou
Country [11] 0 0
China
State/province [11] 0 0
Jinan
Country [12] 0 0
China
State/province [12] 0 0
Linhai
Country [13] 0 0
China
State/province [13] 0 0
Nanchang
Country [14] 0 0
China
State/province [14] 0 0
Nanjing
Country [15] 0 0
China
State/province [15] 0 0
Ningbo
Country [16] 0 0
China
State/province [16] 0 0
Shanghai
Country [17] 0 0
China
State/province [17] 0 0
Shenyang
Country [18] 0 0
China
State/province [18] 0 0
Shijiazhuang
Country [19] 0 0
China
State/province [19] 0 0
Urumqi
Country [20] 0 0
China
State/province [20] 0 0
Wanzhou
Country [21] 0 0
China
State/province [21] 0 0
Wenzhou
Country [22] 0 0
China
State/province [22] 0 0
Wuhan
Country [23] 0 0
China
State/province [23] 0 0
Xi'an
Country [24] 0 0
China
State/province [24] 0 0
Zhengzhou
Country [25] 0 0
China
State/province [25] 0 0
Zhuhai
Country [26] 0 0
Hungary
State/province [26] 0 0
Budapest
Country [27] 0 0
Hungary
State/province [27] 0 0
Deszk
Country [28] 0 0
Hungary
State/province [28] 0 0
Farkasgyepü
Country [29] 0 0
Hungary
State/province [29] 0 0
Gyöngyös - Mátraháza
Country [30] 0 0
Hungary
State/province [30] 0 0
Székesfehérvár
Country [31] 0 0
Hungary
State/province [31] 0 0
Törökbálint
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Changwon-si
Country [33] 0 0
Korea, Republic of
State/province [33] 0 0
Cheongju-si
Country [34] 0 0
Korea, Republic of
State/province [34] 0 0
Daegu
Country [35] 0 0
Korea, Republic of
State/province [35] 0 0
Incheon
Country [36] 0 0
Korea, Republic of
State/province [36] 0 0
Jinju-si
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Seoul
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Suwon-si
Country [39] 0 0
Netherlands
State/province [39] 0 0
Almelo
Country [40] 0 0
Poland
State/province [40] 0 0
Bialystok
Country [41] 0 0
Poland
State/province [41] 0 0
Grudziadz
Country [42] 0 0
Poland
State/province [42] 0 0
Koszalin
Country [43] 0 0
Poland
State/province [43] 0 0
Lublin
Country [44] 0 0
Poland
State/province [44] 0 0
Mrozy
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Poland
State/province [46] 0 0
Wroclaw
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Arkhangelsk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Moscow
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Novosibirsk
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Omsk
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Rostov-on-Don
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Saint Petersburg
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Saint-Petersburg
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Sankt-Peterburg
Country [55] 0 0
Russian Federation
State/province [55] 0 0
St. Petersburg
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Volgograd
Country [57] 0 0
Taiwan
State/province [57] 0 0
Taichung City
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taichung
Country [59] 0 0
Taiwan
State/province [59] 0 0
Taipei
Country [60] 0 0
Thailand
State/province [60] 0 0
Bangkok
Country [61] 0 0
Thailand
State/province [61] 0 0
Muang
Country [62] 0 0
Thailand
State/province [62] 0 0
Songkla
Country [63] 0 0
Turkey
State/province [63] 0 0
Ankara
Country [64] 0 0
Turkey
State/province [64] 0 0
Istanbul
Country [65] 0 0
Turkey
State/province [65] 0 0
Malatya
Country [66] 0 0
Turkey
State/province [66] 0 0
Pamukkale
Country [67] 0 0
Vietnam
State/province [67] 0 0
Can Tho
Country [68] 0 0
Vietnam
State/province [68] 0 0
Hanoi
Country [69] 0 0
Vietnam
State/province [69] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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)
Trial website
https://clinicaltrials.gov/study/NCT03003962
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03003962