Clinical trial NCT03003962: Study of Durvalumab Alone or Chemotherapy for Patients With Advanced Non Small-Cell Lung Cancer (PEARL)
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non Small Cell Lung Carcinoma NSCLC
Keywords: NSCLC
PD-L1
Durvalumab (MEDI4736)
OS
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-12-28
Enrollment: 669
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)

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)

Eligibility 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

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\]

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 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]
measure: OS in Participants With LREM
timeFrame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
Secondary outcomes:
measure: OS in PD-L1 TC >= 50% Analysis Set
timeFrame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
measure: OS in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
measure: Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: 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)
measure: PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set
timeFrame: 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)
measure: PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set
timeFrame: 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)
measure: PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: 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)
measure: Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment
timeFrame: 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)
measure: ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: 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)
measure: ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set
timeFrame: 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)
measure: ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: 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)
measure: Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment
timeFrame: 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)
measure: DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set
timeFrame: 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)
measure: DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set
timeFrame: 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)
measure: DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set
timeFrame: 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)
measure: Alive and Progression-Free at 12 Months (APF12)
timeFrame: From date of randomization until 12 months
measure: APF12 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: From date of randomization until 12 months
measure: APF12 in PD-L1 TC >= 50% Analysis Set
timeFrame: From date of randomization until 12 months
measure: APF12 in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: From date of randomization until 12 months
measure: Time From Randomization to Second Progression (PFS2)
timeFrame: 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)
measure: PFS2 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: 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)
measure: PFS2 in PD-L1 TC >= 50% Analysis Set
timeFrame: 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)
measure: PFS2 in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: 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)
measure: OS at 18 Months
timeFrame: From date of randomization till 18 months.
measure: OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set
timeFrame: From date of randomization till 18 months
measure: OS at 18 Months in PD-L1 TC >= 50% Analysis Set
timeFrame: From date of randomization till 18 months
measure: OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: From date of randomization till 18 months
measure: OS at 24 Months
timeFrame: From date of randomization till 24 months
measure: OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set
timeFrame: From date of randomization till 24 months
measure: OS at 24 Months in PD-L1 TC >= 50% Analysis Set
timeFrame: From date of randomization till 24 months
measure: OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set
timeFrame: From date of randomization till 24 months
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)
timeFrame: Baseline and 12 months
measure: Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: Baseline and 12 months
measure: Time to Deterioration of EORTC QLQ-C30
timeFrame: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
measure: Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)
measure: Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)
timeFrame: Baseline and 12 months
measure: Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: Baseline and 12 months
measure: Time to Deterioration of EORTC QLQ-LC13
timeFrame: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
measure: Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
timeFrame: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)
measure: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: From Baseline and until follow-up period of 57 months
measure: Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set
timeFrame: From Baseline and until follow-up period of 57 months
measure: Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab
timeFrame: Up to 24 weeks
measure: Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: Box Hill
country: Australia
facility: Research Site
city: Gosford
country: Australia
facility: Research Site
city: Kogarah
country: Australia
facility: Research Site
city: St Leonards
country: Australia
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Linhai
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wanzhou
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhuhai
country: China
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Deszk
country: Hungary
facility: Research Site
city: Farkasgyepü
country: Hungary
facility: Research Site
city: Gyöngyös - Mátraháza
country: Hungary
facility: Research Site
city: Székesfehérvár
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Changwon-si
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jinju-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Almelo
country: Netherlands
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Grudziądz
country: Poland
facility: Research Site
city: Koszalin
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Mrozy
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Novosibirsk
country: Russian Federation
facility: Research Site
city: Omsk
country: Russian Federation
facility: Research Site
city: Rostov-on-Don
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Sankt-Peterburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Volgograd
country: Russian Federation
facility: Research Site
city: Taichung City
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Bangkok
country: Thailand
facility: Research Site
city: Muang
country: Thailand
facility: Research Site
city: Songkla
country: Thailand
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Malatya
country: Turkey
facility: Research Site
city: Pamukkale
country: Turkey
facility: Research Site
city: Can Tho
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Hanoi
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
city: Ho Chi Minh
country: Vietnam
facility: Research Site
Study officials:
References: