Clinical trial NCT02542293: Study of Durvalumab With Tremelimumab Versus SoC as 1st Line Therapy in Metastatic Non Small-Cell Lung Cancer (NSCLC) (NEPTUNE)
Official title: A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Non Small Cell Lung Carcinoma NSCLC
Keywords: NSCLC
PDL1
TMB
MEDI4736
Durvalumab
Tremelimumab
OS
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-09-07
Enrollment: 953
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, global, Phase III study to determine the efficacy and safety of durvalumab + tremelimumab combination therapy 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 advanced or metastatic NSCLC.

Detailed description: Patients will be randomized in a 1:1 to receive treatment with durvalumab + tremelimumab combination therapy or SoC therapy. The primary objective of this study is to assess the efficacy of combination treatment compared with SoC in terms of Overall Survival (OS) in patients.

Eligibility criteria: Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

* Aged at least 18 years
* Documented evidence of Stage IV NSCLC
* No activating EGFR mutation or ALK rearrangement
* No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC
* World Health Organization (WHO) Performance Status of 0 or 1
* No Prior exposure to Immune Mediated Therapy (IMT), including, but not limited to, other antiCTLA4, antiPD1, anti PDL1,or antiPDL2 antibodies, excluding therapeutic anticancer vaccines

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

* Mixed small cell lung cancer and NSCLC histology, sarcomatoid variant
* Brain metastases or spinal cord compression unless the patient is stable (asymptomatic; no evidence of new or emerging brain metastases) and off steroids for at least 14 days prior to start of study treatment.
* Active or prior documented autoimmune or inflammatory disorders (e.g., Crohn's disease, ulcerative colitis)

Primary outcomes:
measure: Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set
timeFrame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
measure: OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set
timeFrame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the China cohort DCO date (a maximum of approximately 44 months).
Secondary outcomes:
measure: OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
timeFrame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).
measure: OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets
timeFrame: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort.
measure: Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
measure: PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
measure: Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
measure: ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
measure: Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
measure: DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
measure: Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
measure: APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
timeFrame: Tumour scans performed at baseline then every 6 weeks up to 12 months.
measure: Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).
measure: PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
timeFrame: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.
measure: OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
timeFrame: Months 12, 18 and 24
measure: OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
timeFrame: Months 12, 18 and 24
measure: Serum Concentrations of Durvalumab
timeFrame: Pre-dose and within 1 hour after end of infusion at Week 0 and 12; pre-dose on Week 24 and at follow-up Month 3
measure: Serum Concentrations of Tremelimumab
timeFrame: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3
measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
timeFrame: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
measure: Number of Participants With ADA Response to Tremelimumab
timeFrame: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Santa Rosa
country: United States
facility: Research Site
state: California
city: Louisville
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facility: Research Site
state: Kentucky
city: Florham Park
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facility: Research Site
state: New Jersey
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facility: Research Site
state: New Mexico
city: East Setauket
country: United States
facility: Research Site
state: New York
city: Fresh Meadows
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facility: Research Site
state: New York
city: Poughkeepsie
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facility: Research Site
state: New York
city: Stony Brook
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facility: Research Site
state: New York
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Columbus
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state: Ohio
city: Zanesville
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state: Ohio
city: Pittsburgh
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state: Pennsylvania
city: Houston
country: United States
facility: Research Site
state: Texas
city: Berazategui
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Caba
country: Argentina
facility: Research Site
city: Córdoba
country: Argentina
facility: Research Site
city: La Rioja
country: Argentina
facility: Research Site
city: Rosario
country: Argentina
facility: Research Site
city: San Salvador de Jujuy
country: Argentina
facility: Research Site
city: Santa Rosa
country: Argentina
facility: Research Site
city: Barretos
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Belo Horizonte
country: Brazil
facility: Research Site
city: Fortaleza
country: Brazil
facility: Research Site
city: Ijui
country: Brazil
facility: Research Site
city: Itajai
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Porto Alegre
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: Sao Paulo
country: Brazil
facility: Research Site
city: São José do Rio Preto
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Shumen
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Vratza
country: Bulgaria
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Viña del Mar
country: Chile
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Urumqi
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Oulu
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Heraklion
country: Greece
facility: Research Site
city: Holargos, Athens
country: Greece
facility: Research Site
city: Ioannina
country: Greece
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: King's Park
country: Hong Kong
facility: Research Site
city: Shatin
country: Hong Kong
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: Gurgaon
country: India
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city: Karamsad
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Beer Sheva
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Kfar Saba
country: Israel
facility: Research Site
city: Nahariya
country: Israel
facility: Research Site
city: Petah Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Bunkyo-ku
country: Japan
facility: Research Site
city: Fukushima-shi
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Hirosaki-shi
country: Japan
facility: Research Site
city: Iizuka-shi
country: Japan
facility: Research Site
city: Iwakuni-shi
country: Japan
facility: Research Site
city: Kanazawa
country: Japan
facility: Research Site
city: Kishiwada-shi
country: Japan
facility: Research Site
city: Kobe-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Kyoto-shi
country: Japan
facility: Research Site
city: Mitaka-shi
country: Japan
facility: Research Site
city: Nagaoka-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Niigata-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
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city: Saga-shi
country: Japan
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city: Sagamihara-shi
country: Japan
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city: Sakai-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Tokushima-shi
country: Japan
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city: Ube-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
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city: Yokohama-shi
country: Japan
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city: Yokohama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Hwasun-gun
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuantan
country: Malaysia
facility: Research Site
city: Kuching
country: Malaysia
facility: Research Site
city: Acapulco
country: Mexico
facility: Research Site
city: Aguascalientes
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
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city: Monterrey
country: Mexico
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city: Mérida
country: Mexico
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city: México
country: Mexico
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city: Arequipa
country: Peru
facility: Research Site
city: Bellavista
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Lima
country: Peru
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city: Baguio City
country: Philippines
facility: Research Site
city: Cebu
country: Philippines
facility: Research Site
city: Las Pinas City
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Manila
country: Philippines
facility: Research Site
city: Quezon City
country: Philippines
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Kielce
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Mrozy
country: Poland
facility: Research Site
city: Olsztyn
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wodzisław Śląski
country: Poland
facility: Research Site
city: Łódź
country: Poland
facility: Research Site
city: Amadora
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Doha
country: Qatar
facility: Research Site
city: Suceava
country: Romania
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Omsk
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: St. Petersburg
country: Russian Federation
facility: Research Site
city: Dammam
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Riyadh
country: Saudi Arabia
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Eskilstuna
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Adana
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Ankara
country: Turkey
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: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Chernivtsі
country: Ukraine
facility: Research Site
city: Dnipro
country: Ukraine
facility: Research Site
city: Ivano-Frankivsk
country: Ukraine
facility: Research Site
city: Kapitanivka Village
country: Ukraine
facility: Research Site
city: Kharkiv Region
country: Ukraine
facility: Research Site
city: Kirovohrad
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Lyutizh
country: Ukraine
facility: Research Site
city: Odesa
country: Ukraine
facility: Research Site
city: Sumy
country: Ukraine
facility: Research Site
city: Uzhhorod
country: Ukraine
facility: Research Site
city: Vinnytsia
country: Ukraine
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Faculdade de Medicina da Universidade de São Paulo
name: Gilberto de Castro
role: PRINCIPAL_INVESTIGATOR
References: