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
ARCTIC
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).
2 other identifiers
interventional
597
26 countries
201
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®)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2015
Longer than P75 for phase_3
201 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 13, 2015
CompletedFirst Submitted
Initial submission to the registry
January 28, 2015
CompletedFirst Posted
Study publicly available on registry
February 2, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 9, 2018
CompletedResults Posted
Study results publicly available
April 16, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
August 30, 2023
CompletedJuly 26, 2024
July 1, 2024
3.1 years
January 28, 2015
February 7, 2019
July 25, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Overall Survival (OS)
The OS was defined as the time from the date of randomization until death due to any cause.
From randomization (Day 1) until death due to any cause, approximately 36 months
Progression-Free Survival (PFS)
The PFS was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression. The PFS was determined by Investigator assessments according to response evaluation criteria in solid tumours (RECIST) version 1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 millimeter (mm) or progression of non-target lesions or the appearance of a new lesion
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 (8)
OS, Contribution of the Components Analysis of Sub-study B
From randomization (Day 1) until death due to any cause, approximately 36 months
Percentage of Participants Alive at 12 Months (OS12)
From randomization (Day 1) up to 12 months
PFS, Contribution of the Components Analysis of Sub-study B
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.
Objective Response Rate (ORR)
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.
Duration of Response (DoR)
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.
- +3 more secondary outcomes
Study Arms (6)
MEDI4736 (durvalumab) monotherapy in Sub-study A
EXPERIMENTALMEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
Standard of Care in Sub-study A
ACTIVE COMPARATORInvestigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
MEDI4736 (durvalumab) + tremelimumab in Sub-study B
EXPERIMENTALMEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Standard of Care in Sub-study B
ACTIVE COMPARATORInvestigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
MEDI4736 (durvalumab) monotherapy in Sub-study B
EXPERIMENTALMEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
tremelimumab in Sub-study B
EXPERIMENTALtremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Interventions
MEDI4736 (durvalumab) treatment by intravenous infusion
Vinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.
Gemcitabine by intravenous infusion. Administered at a dose of 1000 mg/m2 iv over 30 minutes on Days 1, 8, and 15 of a 28-day cycle.
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
tremelimumab (anti-CTLA4) treatment by intravenous infusion
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (201)
Research Site
Chandler, Arizona, 85224, United States
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Anaheim, California, 92801, United States
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Duarte, California, 91010, United States
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La Jolla, California, 92093, United States
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San Diego, California, 92123, United States
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Aurora, Colorado, 80045, United States
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Fort Myers, Florida, 33901, United States
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Orlando, Florida, 32804, United States
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Port Saint Lucie, Florida, 34952, United States
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St. Petersburg, Florida, 33705, United States
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Athens, Georgia, 30607, United States
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Atlanta, Georgia, 30322, United States
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Lawrenceville, Georgia, 30046, United States
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Chicago, Illinois, 60612, United States
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Waterloo, Iowa, 50701, United States
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Ashland, Kentucky, 41101, United States
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Rockville, Maryland, 20850, United States
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Battle Creek, Michigan, 49017, United States
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St Louis, Missouri, 63156, United States
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Lincoln, Nebraska, 68506, United States
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Mineola, New York, 11501, United States
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New York, New York, 10011, United States
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New York, New York, 10029, United States
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The Bronx, New York, 10461-2375, United States
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Charlotte, North Carolina, 28204, United States
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Pinehurst, North Carolina, 28374, United States
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Cincinnati, Ohio, 45242, United States
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West Chester, Ohio, 45069, United States
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Chattanooga, Tennessee, 37404, United States
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Germantown, Tennessee, 38138, United States
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Nashville, Tennessee, 37203, United States
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Salt Lake City, Utah, 84106, United States
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Spokane, Washington, 99208, United States
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Murdoch, 6150, Australia
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Port Macquarie, 2444, Australia
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Charleroi, 6000, Belgium
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Ghent, 9000, Belgium
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Libramont-Chevigny, 6800, Belgium
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Mons, 7000, Belgium
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Roeselare, 8800, Belgium
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Yvoir, 5530, Belgium
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Pleven, 5800, Bulgaria
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Sofia, 1330, Bulgaria
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Sofia, 1407, Bulgaria
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Varna, 9010, Bulgaria
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Moncton, New Brunswick, E1C 6Z8, Canada
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Saint John, New Brunswick, E2L 4L2, Canada
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Santiago, 7500000, Chile
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Santiago, 8420383, Chile
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Temuco, 4810469, Chile
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Nová Ves pod Pleší, 262 04, Czechia
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Prague, 128 08, Czechia
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Prague, 150 06, Czechia
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Avignon, 84918, France
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Bayonne, 64100, France
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Brest, 29609, France
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Créteil, 94010, France
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Le Mans, 72000, France
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Marseille, 13915, France
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Montpellier, 34295, France
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Nice, 06100, France
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Pau, 64046, France
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Saint-Herblain, 44805, France
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Toulon, 83100, France
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Villejuif, 94800, France
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Berlin, 10117, Germany
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Berlin, 10967, Germany
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Berlin, 12351, Germany
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Cologne, 51109, Germany
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Dresden, 01307, Germany
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Gauting, 82131, Germany
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Halle, 06120, Germany
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Hamburg, 22081, Germany
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Hanover, 30625, Germany
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Homburg, 66421, Germany
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Löwenstein, 74245, Germany
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Regensburg, 93053, Germany
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Trier, 54290, Germany
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Ulm, 89081, Germany
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Villingen-Schwenningen, 78052, Germany
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Athens, 11527, Greece
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Thessaloniki, 54645, Greece
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Thessaloniki, 57010, Greece
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Hong Kong, Hong Kong
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Miskolc, 3529, Hungary
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Törökbálint, 2045, Hungary
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Zalaegerszeg, 8000, Hungary
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Zalaegerszeg, 8900, Hungary
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Tel Litwinsky, 52621, Israel
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Aviano, 33081, Italy
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Candiolo, 10060, Italy
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Catania, 95123, Italy
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Cremona, 26100, Italy
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Genova, 16100, Italy
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Lucca, 55100, Italy
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Milan, 20132, Italy
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Milan, 20133, Italy
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Milan, 20141, Italy
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Monza, 20900, Italy
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Napoli, 80131, Italy
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Orbassano, 10043, Italy
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Parma, 43100, Italy
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Pisa, 56124, Italy
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Rimini, 47900, Italy
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Terni, 05100, Italy
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Fukuoka, 812-8582, Japan
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Habikino-shi, 583-8588, Japan
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Hidaka-shi, 350-1298, Japan
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Hirakata-shi, 573-1191, Japan
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Hirosaki-shi, 036-8545, Japan
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Hiroshima, 730-8518, Japan
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Kanazawa, 920-8641, Japan
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Kobe, 650-0047, Japan
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Kurume-shi, 830-0011, Japan
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Matsuyama, 791-0280, Japan
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Nagoya, 460-0001, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Natori-shi, 981-1293, Japan
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Okayama, 700-8558, Japan
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Osaka, 541-8567, Japan
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Sakaishi, 591-8555, Japan
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Sapporo, 003-0804, Japan
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Sapporo, 060-8648, Japan
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Sayama, 589-8511, Japan
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Sendai, 980-0873, Japan
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Shinjuku-ku, 160-0023, Japan
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Shinjuku-ku, 162-8655, Japan
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Sunto-gun, 411-8777, Japan
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Takatsuki-shi, 569-8686, Japan
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Wakayama, 641-8510, Japan
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Yokohama, 221-0855, Japan
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Yokohama, 236-0024, Japan
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Amsterdam, 1081 HV, Netherlands
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Lublin, 20-362, Poland
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Poznan, 60-569, Poland
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Warsaw, 02-781, Poland
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Alba Iulia, 510077, Romania
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Baia Mare, 430031, Romania
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Cluj-Napoca, 400132, Romania
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Cluj-Napoca, 400349, Romania
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Onești, 601048, Romania
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Oradea, 410469, Romania
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Timișoara, 300210, Romania
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Arkhangelsk, 163045, Russia
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Omsk, 644013, Russia
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Saint Petersburg, 197002, Russia
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Saint Petersburg, 197022, Russia
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Saint Petersburg, 197758, Russia
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Belgrade, 11000, Serbia
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Gornji Matejevac, 18204, Serbia
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Kamenitz, 21204, Serbia
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Kragujevac, 34000, Serbia
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Singapore, 119074, Singapore
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Singapore, 169610, Singapore
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Singapore, 308433, Singapore
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Busan, 49201, South Korea
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Cheongju-si, 28644, South Korea
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Incheon, 405-760, South Korea
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Jeonnam, 58128, South Korea
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Seongnam-si, 13620, South Korea
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Seoul, 02841, South Korea
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Seoul, 05505, South Korea
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Seoul, 06351, South Korea
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A Coruña, 15006, Spain
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Alicante, 03010, Spain
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Barcelona, 08003, Spain
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Barcelona, 08025, Spain
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Donostia / San Sebastian, 20014, Spain
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Girona, 17007, Spain
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Jaén, 23007, Spain
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Lleida, 25198, Spain
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Madrid, 08035, Spain
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Madrid, 28005, Spain
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Madrid, 28007, Spain
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Madrid, 28033, Spain
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Madrid, 28046, Spain
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Madrid, 28050, Spain
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Seville, 41013, Spain
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Seville, 41071, Spain
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Valencia, 46014, Spain
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Valencia, 46026, Spain
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Taichung, 40447, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 704, Taiwan
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Taipei, 10002, Taiwan
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Taipei, 110, Taiwan
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Taipei, 112, Taiwan
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Taipei, 116, Taiwan
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Taipei, 235, Taiwan
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Bangkok, 10330, Thailand
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Muang, 50200, Thailand
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Phitsanulok, 65000, Thailand
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Songkhla, 90110, Thailand
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Birmingham, B15 2WB, United Kingdom
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London, EC1A 7BE, United Kingdom
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London, W1G 6AD, United Kingdom
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Southampton, SO16 6YD, United Kingdom
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Stevenage, SG1 4AB, United Kingdom
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Truro, TR1 3LJ, United Kingdom
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Wolverhampton, WV10 0QP, United Kingdom
Related Publications (2)
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.
PMID: 34056687DERIVEDPlanchard 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.
PMID: 32201234DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Science Director
- Organization
- AstraZeneca
Study Officials
- STUDY DIRECTOR
Paul Stockman, MBChB, PhD
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2015
First Posted
February 2, 2015
Study Start
January 13, 2015
Primary Completion
February 9, 2018
Study Completion
August 30, 2023
Last Updated
July 26, 2024
Results First Posted
April 16, 2019
Record last verified: 2024-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure