We are experiencing 4 week turn-around time in review of submissions and resubmissions. We recommend commencing this process concurrently with your ethics submission and allowing at least 8 weeks for registration to be completed from date of first submission. We currently do not have the capacity to expedite reviews.

Note also there are delays to review of updates. We appreciate your patience.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03003962
Ethics application status
Date submitted
15/12/2016
Date registered
28/12/2016
Date last updated
3/05/2021

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
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
The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in all randomized patients
Timepoint [1] 0 0
4 years
Primary outcome [2] 0 0
The efficacy of Durvalumab therapy compared to SoC in terms of OS in patients who are at low risk of early mortality (EM)
Timepoint [2] 0 0
4 years
Secondary outcome [1] 0 0
The efficacy of Durvalumab compared to SoC in terms of Objective response rate (ORR)
Timepoint [1] 0 0
4 years
Secondary outcome [2] 0 0
The efficacy of Durvalumab compared to SoC in terms of Duration of response (DoR)
Timepoint [2] 0 0
4 years
Secondary outcome [3] 0 0
The efficacy of Durvalumab compared to SoC in terms of A Proportion of patients alive and progression free at 12 months from randomization (APF12)
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
The efficacy of Durvalumab compared to SoC in terms of Progression-free survival after subsequent anticancer therapy (PFS2)
Timepoint [4] 0 0
4 years
Secondary outcome [5] 0 0
Disease-related symptoms and health-related quality of life in subjects treated with durvalumab compared to SoC using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
Timepoint [5] 0 0
4 years
Secondary outcome [6] 0 0
The immunogenicity of durvalumab by measuring the presence of Anti-drug Antibodies
Timepoint [6] 0 0
4 years
Secondary outcome [7] 0 0
The efficacy of Durvalumab therapy compared to SoC in terms of progress-free survival (PFS) in patients with NSCLC
Timepoint [7] 0 0
4 years
Secondary outcome [8] 0 0
The efficacy of Durvalumab therapy compared to SoC in terms of Overall Survival (OS) in PD-L1 high patients and in PD-L1 high with low risk of EM population
Timepoint [8] 0 0
4 years
Secondary outcome [9] 0 0
Proportion of patients alive at 18 months from randomization (OS18)
Timepoint [9] 0 0
18 months
Secondary outcome [10] 0 0
Proportion of patients alive at 24 months from randomization (OS24)
Timepoint [10] 0 0
24 months

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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Changchun
Country [4] 0 0
China
State/province [4] 0 0
Changsha
Country [5] 0 0
China
State/province [5] 0 0
Chengdu
Country [6] 0 0
China
State/province [6] 0 0
Guangzhou
Country [7] 0 0
China
State/province [7] 0 0
Haikou
Country [8] 0 0
China
State/province [8] 0 0
Hangzhou
Country [9] 0 0
China
State/province [9] 0 0
Jinan
Country [10] 0 0
China
State/province [10] 0 0
Nanchang
Country [11] 0 0
China
State/province [11] 0 0
Ningbo
Country [12] 0 0
China
State/province [12] 0 0
Shanghai
Country [13] 0 0
China
State/province [13] 0 0
Shenyang
Country [14] 0 0
China
State/province [14] 0 0
Shijiazhuang
Country [15] 0 0
China
State/province [15] 0 0
Urumqi
Country [16] 0 0
China
State/province [16] 0 0
Wuhan
Country [17] 0 0
China
State/province [17] 0 0
Xi'an
Country [18] 0 0
China
State/province [18] 0 0
Zhengzhou
Country [19] 0 0
Hungary
State/province [19] 0 0
Budapest
Country [20] 0 0
Hungary
State/province [20] 0 0
Deszk
Country [21] 0 0
Hungary
State/province [21] 0 0
Farkasgyepü
Country [22] 0 0
Hungary
State/province [22] 0 0
Mátraháza
Country [23] 0 0
Hungary
State/province [23] 0 0
Székesfehérvár
Country [24] 0 0
Hungary
State/province [24] 0 0
Törökbálint
Country [25] 0 0
Korea, Republic of
State/province [25] 0 0
Changwon-si
Country [26] 0 0
Korea, Republic of
State/province [26] 0 0
Cheongju-si
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Daegu
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Incheon
Country [29] 0 0
Korea, Republic of
State/province [29] 0 0
Jinju-si
Country [30] 0 0
Korea, Republic of
State/province [30] 0 0
Seoul
Country [31] 0 0
Korea, Republic of
State/province [31] 0 0
Suwon-si
Country [32] 0 0
Netherlands
State/province [32] 0 0
Almelo
Country [33] 0 0
Poland
State/province [33] 0 0
Bialystok
Country [34] 0 0
Poland
State/province [34] 0 0
Grudziadz
Country [35] 0 0
Poland
State/province [35] 0 0
Koszalin
Country [36] 0 0
Poland
State/province [36] 0 0
Lublin
Country [37] 0 0
Poland
State/province [37] 0 0
Mrozy
Country [38] 0 0
Poland
State/province [38] 0 0
Warszawa
Country [39] 0 0
Poland
State/province [39] 0 0
Wroclaw
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Arkhangelsk
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Moscow
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Novosibirsk
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Omsk
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Rostov-on-Don
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Saint Petersburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saint-Petersburg
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Sankt-Peterburg
Country [48] 0 0
Russian Federation
State/province [48] 0 0
St. Petersburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Volgograd
Country [50] 0 0
Taiwan
State/province [50] 0 0
Taichung City
Country [51] 0 0
Taiwan
State/province [51] 0 0
Taichung
Country [52] 0 0
Taiwan
State/province [52] 0 0
Taipei
Country [53] 0 0
Thailand
State/province [53] 0 0
Bangkok
Country [54] 0 0
Thailand
State/province [54] 0 0
Muang
Country [55] 0 0
Thailand
State/province [55] 0 0
Songkla
Country [56] 0 0
Turkey
State/province [56] 0 0
Ankara
Country [57] 0 0
Turkey
State/province [57] 0 0
Istanbul
Country [58] 0 0
Turkey
State/province [58] 0 0
Malatya
Country [59] 0 0
Turkey
State/province [59] 0 0
Pamukkale
Country [60] 0 0
Vietnam
State/province [60] 0 0
Can Tho
Country [61] 0 0
Vietnam
State/province [61] 0 0
Hanoi
Country [62] 0 0
Vietnam
State/province [62] 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/show/NCT03003962
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Shire Norah
Address 0 0
AstraZeneca GMD IO, Gaitherburg, MD, USA
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
Other publications