Clinical trial NCT02352948: A Global Study to Assess the Effects of MEDI4736 (Durvalumab), Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer
Official title: A Phase III, Open Label, Randomised, Multi-centre, International Study of MEDI4736, Given as Monotherapy or in Combination With Tremelimumab Determined by PD-L1 Expression Versus Standard of Care in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Stage IIIB-IV) Who Have Received at Least Two Prior Systemic Treatment Regimens Including One Platinum Based Chemotherapy Regimen and Do Not Have Known EGFR TK Activating Mutations or ALK Rearrangements (ARCTIC).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non - Small Cell Lung Cancer NSCLC
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-02-02
Enrollment: 597
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 study is a Phase III, randomised, open label, multi-centre study assessing the efficacy and safety of MEDI4736 (durvalumab) versus Standard of Care in NSCLC patients with PD-L1 positive tumours and the combination of MEDI4736 (durvalumab) plus tremelimumab (MEDI4736+treme) versus Standard of Care in NSCLC patients with PD-L1-negative tumours in the treatment of male and female patients with locally advanced or metastatic NSCLC (Stage IIIB-IV), who have received at least 2 prior systemic treatment regimens including 1 platinum-based chemotherapy regimen for NSCLC. Patients with known EGFR (Epidermal growth factor receptor) tyrosine kinase (TK) activating mutations and anaplastic lymphoma kinase (ALK) rearrangements are not eligible for the study (prospective testing is not planned within this study). The Standard of Care options are: an EGFR tyrosine kinase inhibitor (erlotinib \[TARCEVA®\]), gemcitabine or vinorelbine (NAVELBINE®)

Detailed description: The study has an umbrella design with 2 sub-studies: sub-study A (randomizing patients with PD-L1 positive tumours 1:1 into MEDI4736 (durvalumab) vs. Standard of Care) and sub-study B (randomizing patients with PD-L1 negative tumours 2:3:1:2 into MEDI4736 (durvalumab) vs. MEDI4736 (durvalumab) plus tremelimumab vs. tremelimumab vs. Standard of Care. The two substudies may have different durations of recruitment periods due to differences in patient population (PD-L1 expression). They may not run concurrently with start and completion of recruitment potentially occurring at different time points.

Eligibility criteria: Inclusion Criteria:

* Aged at least 18 years
* Documented evidence of NSCLC (Stage IIIB/ IV disease)
* Disease progression or recurrence after both a platinum-based chemotherapy regimen and at least 1 additional regimen for treatment of NSCLC
* World Health Organization (WHO) Performance Status of 0 or 1
* Estimated life expectancy more than 12 weeks

Exclusion Criteria:

* Prior exposure to any anti-PD-1 or anti-PD-L1 antibody or anti-CTLA4
* Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
* Active or prior documented autoimmune disease within the past 2 years
* Evidence of severe or uncontrolled systemic disease, including active bleeding diatheses or active infections including hepatitis B, C and HIV
* Any unresolved toxicity CTCAE (Common Terminology Criteria of Adverse Events) \>Grade 2 from previous anti-cancer therapy
* Known EGFR TK activating mutations or ALK rearrangements
* Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
* Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization (Day 1) until death due to any cause, approximately 36 months
measure: Progression-Free Survival (PFS)
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
Secondary outcomes:
measure: OS, Contribution of the Components Analysis of Sub-study B
timeFrame: From randomization (Day 1) until death due to any cause, approximately 36 months
measure: Percentage of Participants Alive at 12 Months (OS12)
timeFrame: From randomization (Day 1) up to 12 months
measure: PFS, Contribution of the Components Analysis of Sub-study B
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
measure: Objective Response Rate (ORR)
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
measure: Duration of Response (DoR)
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed up to a maximum of approximately 3 years.
measure: Percentage of Participants Alive and Progression Free at 6 Months (APF6)
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 6 months
measure: Percentage of Participants Alive and Progression Free at 12 Months (APF12)
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 12 months.
measure: Time From Randomisation to Second Progression (PFS2) of Sub-study B
timeFrame: Tumour scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until first progression. Disease then assessed per local practice until 2nd progression. Assessed up to a maximum of approximately 3 years.
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Research Site
state: Arizona
city: Anaheim
country: United States
facility: Research Site
state: California
city: Duarte
country: United States
facility: Research Site
state: California
city: La Jolla
country: United States
facility: Research Site
state: California
city: San Diego
country: United States
facility: Research Site
state: California
city: Aurora
country: United States
facility: Research Site
state: Colorado
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Port Saint Lucie
country: United States
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state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Waterloo
country: United States
facility: Research Site
state: Iowa
city: Ashland
country: United States
facility: Research Site
state: Kentucky
city: Rockville
country: United States
facility: Research Site
state: Maryland
city: Battle Creek
country: United States
facility: Research Site
state: Michigan
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Bronx
country: United States
facility: Research Site
state: New York
city: Mineola
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Pinehurst
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: West Chester
country: United States
facility: Research Site
state: Ohio
city: Chattanooga
country: United States
facility: Research Site
state: Tennessee
city: Germantown
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
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state: Tennessee
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Murdoch
country: Australia
facility: Research Site
city: Port Macquarie
country: Australia
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Libramont-Chevigny
country: Belgium
facility: Research Site
city: Mons
country: Belgium
facility: Research Site
city: Roeselare
country: Belgium
facility: Research Site
city: Yvoir
country: Belgium
facility: Research Site
city: Pleven
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: Moncton
country: Canada
facility: Research Site
state: New Brunswick
city: Saint John
country: Canada
facility: Research Site
state: New Brunswick
city: Santiago
country: Chile
facility: Research Site
city: Santiago
country: Chile
facility: Research Site
city: Temuco
country: Chile
facility: Research Site
city: Nova Ves pod Plesi
country: Czechia
facility: Research Site
city: Praha 2
country: Czechia
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Avignon Cedex 9
country: France
facility: Research Site
city: Bayonne
country: France
facility: Research Site
city: Brest Cedex
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Le Mans
country: France
facility: Research Site
city: Marseille Cedex 20
country: France
facility: Research Site
city: Montpellier Cedex
country: France
facility: Research Site
city: Nice
country: France
facility: Research Site
city: Pau Cedex
country: France
facility: Research Site
city: Saint Herblain
country: France
facility: Research Site
city: Toulon
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dresden
country: Germany
facility: Research Site
city: Gauting
country: Germany
facility: Research Site
city: Halle
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Hannover
country: Germany
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city: Homburg
country: Germany
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city: Köln
country: Germany
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city: Löwenstein
country: Germany
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city: Regensburg
country: Germany
facility: Research Site
city: Trier
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Villingen-Schwenningen
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Törökbálint
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Zalaegerszeg
country: Hungary
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Aviano
country: Italy
facility: Research Site
city: Candiolo
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Cremona
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Lucca
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Monza
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Orbassano
country: Italy
facility: Research Site
city: Parma
country: Italy
facility: Research Site
city: Pisa
country: Italy
facility: Research Site
city: Rimini
country: Italy
facility: Research Site
city: Terni
country: Italy
facility: Research Site
city: Fukuoka-shi
country: Japan
facility: Research Site
city: Habikino-shi
country: Japan
facility: Research Site
city: Hidaka-shi
country: Japan
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city: Hirakata-shi
country: Japan
facility: Research Site
city: Hirosaki-shi
country: Japan
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city: Hiroshima-shi
country: Japan
facility: Research Site
city: Kanazawa
country: Japan
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city: Kobe-shi
country: Japan
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city: Kurume-shi
country: Japan
facility: Research Site
city: Matsuyama-shi
country: Japan
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city: Nagoya-shi
country: Japan
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city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Natori-shi
country: Japan
facility: Research Site
city: Okayama-shi
country: Japan
facility: Research Site
city: Osaka-shi
country: Japan
facility: Research Site
city: Osakasayama
country: Japan
facility: Research Site
city: Sakai-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Sendai-shi
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
city: Sunto-gun
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Wakayama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Jeonnam
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Alba Iulia
country: Romania
facility: Research Site
city: Baia Mare
country: Romania
facility: Research Site
city: Cluj Napoca
country: Romania
facility: Research Site
city: Cluj-Napoca
country: Romania
facility: Research Site
city: Onesti
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Timisoara
country: Romania
facility: Research Site
city: Arkhangelsk
country: Russian Federation
facility: Research Site
city: Omsk
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: St. Petersburg
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Belgrad
country: Serbia
facility: Research Site
city: Gornji Matejevac
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Sremska Kamenica
country: Serbia
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: A Coruña
country: Spain
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Girona
country: Spain
facility: Research Site
city: Jaén
country: Spain
facility: Research Site
city: Lleida
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: San Sebastian
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
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: Muang
country: Thailand
facility: Research Site
city: Phitsanulok
country: Thailand
facility: Research Site
city: Songkla
country: Thailand
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
city: Stevenage
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Paul Stockman, MBChB, PhD
role: STUDY_DIRECTOR
References:
citation: Martin ML, Correll J, Walding A, Ryden A. How patients being treated for non-small cell lung cancer value treatment benefit despite side effects. Qual Life Res. 2022 Jan;31(1):135-146. doi: 10.1007/s11136-021-02882-6. Epub 2021 May 31.
citation: Planchard D, Reinmuth N, Orlov S, Fischer JR, Sugawara S, Mandziuk S, Marquez-Medina D, Novello S, Takeda Y, Soo R, Park K, McCleod M, Geater SL, Powell M, May R, Scheuring U, Stockman P, Kowalski D. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. doi: 10.1016/j.annonc.2020.02.006. Epub 2020 Feb 20.