Non - Small Cell Lung Cancer NSCLCPhase 3ARCTICNCT02352948

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

A Phase 3 study testing MEDI4736 (durvalumab), Vinorelbine and Gemcitabine in people with Non - Small Cell Lung Cancer NSCLC, run by AstraZeneca at 201 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 130 years
Conditions the study is for: Non - Small Cell Lung Cancer NSCLC
What is being tested?: MEDI4736 (durvalumab), Vinorelbine and Gemcitabine
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 597 participants
Where: 201 sitesin 26 countries
Study dates: 13 Jan 2015to 30 Aug 2023
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 130 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Trial locations and contacts

201 sites in 26 countries.

Country

City, postcode or hospital

201 sites in 26 countries

United States33 sites

Research Site
Anaheim, California, 92801
Research Site
Ashland, Kentucky, 41101
Research Site
Athens, Georgia, 30607
Research Site
Atlanta, Georgia, 30322
Research Site
Aurora, Colorado, 80045
Research Site
Battle Creek, Michigan, 49017
Research Site
Chandler, Arizona, 85224
Research Site
Charlotte, North Carolina, 28204
Research Site
Chattanooga, Tennessee, 37404
Research Site
Chicago, Illinois, 60612
Research Site
Cincinnati, Ohio, 45242
Research Site
Duarte, California, 91010
Research Site
Fort Myers, Florida, 33901
Research Site
Germantown, Tennessee, 38138
Research Site
La Jolla, California, 92093
Research Site
Lawrenceville, Georgia, 30046
Research Site
Lincoln, Nebraska, 68506
Research Site
Mineola, New York, 11501
Research Site
Nashville, Tennessee, 37203
Research Site
New York, New York, 10011
Research Site
New York, New York, 10029
Research Site
Orlando, Florida, 32804
Research Site
Pinehurst, North Carolina, 28374
Research Site
Port Saint Lucie, Florida, 34952
Research Site
Rockville, Maryland, 20850
Research Site
Salt Lake City, Utah, 84106
Research Site
San Diego, California, 92123
Research Site
Spokane, Washington, 99208
Research Site
St Louis, Missouri, 63156
Research Site
St. Petersburg, Florida, 33705
Research Site
The Bronx, New York, 10461-2375
Research Site
Waterloo, Iowa, 50701
Research Site
West Chester, Ohio, 45069

Other trials in United States

Japan28 sites

Research Site
Fukuoka, 812-8582
Research Site
Habikino-shi, 583-8588
Research Site
Hidaka-shi, 350-1298
Research Site
Hirakata-shi, 573-1191
Research Site
Hirosaki-shi, 036-8545
Research Site
Hiroshima, 730-8518
Research Site
Kanazawa, 920-8641
Research Site
Kobe, 650-0047
Research Site
Kurume-shi, 830-0011
Research Site
Matsuyama, 791-0280
Research Site
Nagoya, 460-0001
Research Site
Nagoya, 464-8681
Research Site
Nagoya, 466-8560
Research Site
Natori-shi, 981-1293
Research Site
Okayama, 700-8558
Research Site
Osaka, 541-8567
Research Site
Sakaishi, 591-8555
Research Site
Sapporo, 003-0804
Research Site
Sapporo, 060-8648
Research Site
Sayama, 589-8511
Research Site
Sendai, 980-0873
Research Site
Shinjuku-ku, 160-0023
Research Site
Shinjuku-ku, 162-8655
Research Site
Sunto-gun, 411-8777
Research Site
Takatsuki-shi, 569-8686
Research Site
Wakayama, 641-8510
Research Site
Yokohama, 221-0855
Research Site
Yokohama, 236-0024

Other trials in Japan

Spain18 sites

Research Site
A Coruña, 15006
Research Site
Alicante, 03010
Research Site
Barcelona, 08003
Research Site
Barcelona, 08025
Research Site
Donostia / San Sebastian, 20014
Research Site
Girona, 17007
Research Site
Jaén, 23007
Research Site
Lleida, 25198
Research Site
Madrid, 08035
Research Site
Madrid, 28005
Research Site
Madrid, 28007
Research Site
Madrid, 28033
Research Site
Madrid, 28046
Research Site
Madrid, 28050
Research Site
Seville, 41013
Research Site
Seville, 41071
Research Site
Valencia, 46014
Research Site
Valencia, 46026

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Italy16 sites

Research Site
Aviano, 33081
Research Site
Candiolo, 10060
Research Site
Catania, 95123
Research Site
Cremona, 26100
Research Site
Genova, 16100
Research Site
Lucca, 55100
Research Site
Milan, 20132
Research Site
Milan, 20133
Research Site
Milan, 20141
Research Site
Monza, 20900
Research Site
Naples, 80131
Research Site
Orbassano, 10043
Research Site
Parma, 43100
Research Site
Pisa, 56124
Research Site
Rimini, 47900
Research Site
Terni, 05100

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Germany15 sites

Research Site
Berlin, 10117
Research Site
Berlin, 10967
Research Site
Berlin, 12351
Research Site
Cologne, 51109
Research Site
Dresden, 01307
Research Site
Gauting, 82131
Research Site
Halle, 06120
Research Site
Hamburg, 22081
Research Site
Hanover, 30625
Research Site
Homburg, 66421
Research Site
Löwenstein, 74245
Research Site
Regensburg, 93053
Research Site
Trier, 54290
Research Site
Ulm, 89081
Research Site
Villingen-Schwenningen, 78052

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France12 sites

Research Site
Avignon, 84918
Research Site
Bayonne, 64100
Research Site
Brest, 29609
Research Site
Créteil, 94010
Research Site
Le Mans, 72000
Research Site
Marseille, 13915
Research Site
Montpellier, 34295
Research Site
Nice, 06100
Research Site
Pau, 64046
Research Site
Saint-Herblain, 44805
Research Site
Toulon, 83100
Research Site
Villejuif, 94800

Other trials in France

South Korea8 sites

Research Site
Busan, 49201
Research Site
Cheongju-si, 28644
Research Site
Incheon, 405-760
Research Site
Jeonnam, 58128
Research Site
Seongnam-si, 13620
Research Site
Seoul, 02841
Research Site
Seoul, 05505
Research Site
Seoul, 06351

Other trials in South Korea

Taiwan8 sites

Research Site
Taichung, 40447
Research Site
Taichung, 40705
Research Site
Tainan, 704
Research Site
Taipei, 10002
Research Site
Taipei, 110
Research Site
Taipei, 112
Research Site
Taipei, 116
Research Site
Taipei, 235

Other trials in Taiwan

Romania7 sites

Research Site
Alba Iulia, 510077
Research Site
Baia Mare, 430031
Research Site
Cluj-Napoca, 400132
Research Site
Cluj-Napoca, 400349
Research Site
Onești, 601048
Research Site
Oradea, 410469
Research Site
Timișoara, 300210

Other trials in Romania

United Kingdom7 sites

Research Site
Birmingham, B15 2WB
Research Site
London, EC1A 7BE
Research Site
London, W1G 6AD
Research Site
Southampton, SO16 6YD
Research Site
Stevenage, SG1 4AB
Research Site
Truro, TR1 3LJ
Research Site
Wolverhampton, WV10 0QP

Other trials in United Kingdom

Belgium6 sites

Research Site
Charleroi, 6000
Research Site
Ghent, 9000
Research Site
Libramont-Chevigny, 6800
Research Site
Mons, 7000
Research Site
Roeselare, 8800
Research Site
Yvoir, 5530

Other trials in Belgium

Russia5 sites

Research Site
Arkhangelsk, 163045
Research Site
Omsk, 644013
Research Site
Saint Petersburg, 197002
Research Site
Saint Petersburg, 197022
Research Site
Saint Petersburg, 197758

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Bulgaria4 sites

Research Site
Pleven, 5800
Research Site
Sofia, 1330
Research Site
Sofia, 1407
Research Site
Varna, 9010

Other trials in Bulgaria

Hungary4 sites

Research Site
Miskolc, 3529
Research Site
Törökbálint, 2045
Research Site
Zalaegerszeg, 8000
Research Site
Zalaegerszeg, 8900

Other trials in Hungary

Serbia4 sites

Research Site
Belgrade, 11000
Research Site
Gornji Matejevac, 18204
Research Site
Kamenitz, 21204
Research Site
Kragujevac, 34000

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Thailand4 sites

Research Site
Bangkok, 10330
Research Site
Muang, 50200
Research Site
Phitsanulok, 65000
Research Site
Songkhla, 90110

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Chile3 sites

Research Site
Santiago, 7500000
Research Site
Santiago, 8420383
Research Site
Temuco, 4810469

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Czechia3 sites

Research Site
Nová Ves pod Pleší, 262 04
Research Site
Prague, 128 08
Research Site
Prague, 150 06

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Greece3 sites

Research Site
Athens, 11527
Research Site
Thessaloniki, 54645
Research Site
Thessaloniki, 57010

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Poland3 sites

Research Site
Lublin, 20-362
Research Site
Poznan, 60-569
Research Site
Warsaw, 02-781

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Singapore3 sites

Research Site
Singapore, 119074
Research Site
Singapore, 169610
Research Site
Singapore, 308433

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Australia2 sites

Research Site
Murdoch, 6150
Research Site
Port Macquarie, 2444

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Canada2 sites

Research Site
Moncton, New Brunswick, E1C 6Z8
Research Site
Saint John, New Brunswick, E2L 4L2

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Hong Kong1 site

Research Site
Hong Kong

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Israel1 site

Research Site
Tel HaShomer, 52621

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Netherlands1 site

Research Site
Amsterdam, 1081 HV

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About this study

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).

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®)

Read the 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.

Conditions: Non - Small Cell Lung Cancer NSCLC
Being tested: MEDI4736 (durvalumab), Vinorelbine, Gemcitabine, Erlotinib, MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MEDI4736 (durvalumab)Drug
MEDI4736 (durvalumab) treatment by intravenous infusion
VinorelbineDrug
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.
GemcitabineDrug
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.
ErlotinibDrug
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)Drug
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
tremelimumab (anti-CTLA4)Drug
tremelimumab (anti-CTLA4) treatment by intravenous infusion

Study groups in NCT02352948
Study group	Role	What they receive
MEDI4736 (durvalumab) monotherapy in Sub-study A	Experimental	MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors. Receives: Drug: MEDI4736 (durvalumab)
Standard of Care in Sub-study A	Active comparator	Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors. Receives: Drug: Vinorelbine; Drug: Gemcitabine; Drug: Erlotinib
MEDI4736 (durvalumab) + tremelimumab in Sub-study B	Experimental	MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors. Receives: Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
Standard of Care in Sub-study B	Active comparator	Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors. Receives: Drug: Vinorelbine; Drug: Gemcitabine; Drug: Erlotinib
MEDI4736 (durvalumab) monotherapy in Sub-study B	Experimental	MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors. Receives: Drug: MEDI4736 (durvalumab)
tremelimumab in Sub-study B	Experimental	tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors. Receives: Drug: tremelimumab (anti-CTLA4)

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival (OS)
The OS was defined as the time from the date of randomization until death due to any cause.
Measured: 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
Measured: 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
The OS was defined as the time from the date of randomization until death due to any cause.
Measured: From randomization (Day 1) until death due to any cause, approximately 36 months
Percentage of Participants Alive at 12 Months (OS12)
The OS12 was defined as the percentage of participants who were alive at 12 months after randomisation per Kaplan-Meier estimate of OS at 12 months.
Measured: From randomization (Day 1) up to 12 months
PFS, Contribution of the Components Analysis of Sub-study B
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 RECIST v1.1. 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
Measured: 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)
The ORR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) among ITT participants who had measurable disease at baseline. CR was defined as disappearance of all target lesions (any pathological lymph nodes selected as target lesions must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum of diameters as long as criteria for PD are not met). The ORR was measured using Investigator assessments according to RECIST v1.1.
Measured: 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)
The DoR was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression. The DoR was determined by Investigator assessments according to RECIST v1.1. 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
Measured: 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.
Percentage of Participants Alive and Progression Free at 6 Months (APF6)
The APF6 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 6 months after randomization per Kaplan-Meier estimate of PFS at 6 months. 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
Measured: Tumour scans performed at baseline then every ~8 weeks up to 6 months
Percentage of Participants Alive and Progression Free at 12 Months (APF12)
The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months. 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
Measured: Tumour scans performed at baseline then every ~8 weeks up to 12 months.
Time From Randomisation to Second Progression (PFS2) of Sub-study B
The PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to that used for the PFS endpoint or death and determined by local standard clinical practice and have included any of the following: objective radiological, symptomatic progression, or death. PFS2 was reported for sub-study B only.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Jan 201530 Aug 2023

First posted2 Feb 2015 (estimated)
Study start13 Jan 2015
Primary completion9 Feb 2018
Study completion30 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Non - Small Cell Lung Cancer NSCLCStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 597 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02352948
Sponsor's protocol ID: D4191C00004
Other IDs: 2014-000338-46, 2014
Acronym: ARCTIC
Status last verified: Jul 2024
First submitted: 28 Jan 2015
Last updated: 26 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Yes: 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

Publications

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.
PubMed 34056687
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.
PubMed 32201234

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 26 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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).
ClinicalTrials.gov ID: NCT02352948
Acronym / sponsor ID: ARCTIC / D4191C00004
Conditions: Non - Small Cell Lung Cancer NSCLC
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 597 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 13 Jan 2015 (actual)
Primary completion: 9 Feb 2018 (actual)
Study completion: 30 Aug 2023 (actual)
First posted: 2 Feb 2015 (estimated)
Results: Posted 16 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
MEDI4736 (durvalumab) monotherapy in Sub-study A	Experimental	Drug: MEDI4736 (durvalumab)MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
Standard of Care in Sub-study A	Active comparator	Drug: Vinorelbine, Drug: Gemcitabine, Drug: ErlotinibInvestigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
MEDI4736 (durvalumab) + tremelimumab in Sub-study B	Experimental	Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)MEDI4736 (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 comparator	Drug: Vinorelbine, Drug: Gemcitabine, Drug: ErlotinibInvestigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
MEDI4736 (durvalumab) monotherapy in Sub-study B	Experimental	Drug: MEDI4736 (durvalumab)MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
tremelimumab in Sub-study B	Experimental	Drug: tremelimumab (anti-CTLA4)tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.

Who may qualify

Ages: 18 to 130 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (8 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MEDI4736 (durvalumab)MEDI4736 (durvalumab) treatment by intravenous infusion	Drug	MEDI4736 (durvalumab) monotherapy in Sub-study A, MEDI4736 (durvalumab) monotherapy in Sub-study B
VinorelbineVinorelbine by intravenous infusion. Administered at a dose of 30 mg/m2 iv on Days 1, 8, 15 and 22 of a 28-day cycle.	Drug	Standard of Care in Sub-study A, Standard of Care in Sub-study B
GemcitabineGemcitabine 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.	Drug	Standard of Care in Sub-study A, Standard of Care in Sub-study B
ErlotinibErlotinib administered at a dose of 150 mg once daily as a tablet for oral administration	Drug	Standard of Care in Sub-study A, Standard of Care in Sub-study B
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion	Drug	MEDI4736 (durvalumab) + tremelimumab in Sub-study B
tremelimumab (anti-CTLA4)tremelimumab (anti-CTLA4) treatment by intravenous infusion	Drug	tremelimumab in Sub-study B

Primary outcome

Overall Survival (OS)
Time frame: From randomization (Day 1) until death due to any cause, approximately 36 months
The OS was defined as the time from the date of randomization until death due to any cause.
Progression-Free Survival (PFS)
Time frame: 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.
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

8 secondary outcomes

OS, Contribution of the Components Analysis of Sub-study B
Time frame: From randomization (Day 1) until death due to any cause, approximately 36 months
Percentage of Participants Alive at 12 Months (OS12)
Time frame: From randomization (Day 1) up to 12 months
PFS, Contribution of the Components Analysis of Sub-study B
Time frame: 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)
Time frame: 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)
Time frame: 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.
Percentage of Participants Alive and Progression Free at 6 Months (APF6)
Time frame: Tumour scans performed at baseline then every ~8 weeks up to 6 months
Percentage of Participants Alive and Progression Free at 12 Months (APF12)
Time frame: Tumour scans performed at baseline then every ~8 weeks up to 12 months.
Time From Randomisation to Second Progression (PFS2) of Sub-study B
Time frame: 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.

Results and safety

Results posted to the registry on 16 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sub-study A: Durvalumab	62	13
Sub-study A: Standard of Care (SoC)	64	5
Sub-study B: Durvalumab+Tremelimumab	174	45
Sub-study B: SoC	118	19
Sub-study B: Durvalumab	117	29
Sub-study B: Tremelimumab	60	11

Primary outcome: Overall Survival (OS)

Time frame: From randomization (Day 1) until death due to any cause, approximately 36 months. Median (95% Confidence Interval). Unit: months

Measure	Sub-study A: Durvalumab n = 62	Sub-study A: SoC n = 64	Sub-study B: Durvalumab+Tremelimumab n = 174	Sub-study B: SoC n = 118
Value	11.7 (8.2 to 17.4)	6.8 (4.9 to 10.2)	11.5 (8.7 to 14.1)	8.7 (6.5 to 11.7)

Sub-study A: Durvalumab vs Sub-study A: SoC: Hazard Ratio (HR): 0.63 (95% CI 0.42 to 0.93)
Sub-study B: Durvalumab+Tremelimumab vs Sub-study B: SoC: Hazard Ratio (HR): 0.80 (95% CI 0.61 to 1.05), p = 0.109, Log Rank

Population analysed: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.

Primary outcome: Progression-Free Survival (PFS)

Time frame: 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.. Median (95% Confidence Interval). Unit: months

Measure	Sub-study A: Durvalumab n = 62	Sub-study A: SoC n = 64	Sub-study B: Durvalumab+Tremelimumab n = 174	Sub-study B: SoC n = 118
Value	3.8 (1.9 to 5.6)	2.2 (1.9 to 3.7)	3.5 (2.3 to 4.6)	3.5 (1.9 to 3.9)

Sub-study A: Durvalumab vs Sub-study A: SoC: Hazard Ratio (HR): 0.71 (95% CI 0.49 to 1.04)
Sub-study B: Durvalumab+Tremelimumab vs Sub-study B: SoC: Hazard Ratio (HR): 0.77 (95% CI 0.59 to 1.01), p = 0.056, Log Rank

Population analysed: Sub-study A and B: FAS included all randomized participants analyzed on an ITT basis.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: From signature of informed consent up to 90 days after the last dose of durvalumab and/or tremelimumab and 30 days after the last dose of SoC, approximately 15 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sub-study A: Durvalumab	23 of 62 (37.1%)	52 of 62 (83.9%)	48 of 62
Sub-study A: SoC	16 of 63 (25.4%)	59 of 63 (93.7%)	55 of 64
Sub-study B: Durvalumab+Tremelimumab	65 of 173 (37.6%)	139 of 173 (80.3%)	118 of 174
Sub-study B: SoC	28 of 110 (25.5%)	100 of 110 (90.9%)	90 of 118
Sub-study B: Durvalumab	36 of 117 (30.8%)	99 of 117 (84.6%)	83 of 117
Sub-study B: Tremelimumab	23 of 60 (38.3%)	48 of 60 (80%)	46 of 60

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34056687Martin 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.
Derived from this study: PubMed 32201234Planchard 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.
AstraZeneca Cancer Study Locator Service astrazeneca@emergingmed.com Phone number: 1-877-400-465Link provided by the sponsor.
Redacted SAPLink provided by the sponsor.
Redacted CSPLink provided by the sponsor.
CSR Synopsis redactedLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Paul Stockman, MBChB, PhD study director

AstraZeneca

201 sites in 26 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MEDI4736 (durvalumab), Vinorelbine and Gemcitabine in people with Non - Small Cell Lung Cancer NSCLC, run by AstraZeneca at 201 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 201 sites in United States, Japan, Spain, Italy, Germany and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: From randomization (Day 1) until death due to any cause, approximately 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02352948, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2024.