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)

July 25, 2024 updated by: AstraZeneca

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®)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
597

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Murdoch, Australia, 6150
        • Research Site
      • Port Macquarie, Australia, 2444
        • Research Site
  • Belgium
      • Charleroi, Belgium, 6000
        • Research Site
      • Gent, Belgium, 9000
        • Research Site
      • Libramont-Chevigny, Belgium, 6800
        • Research Site
      • Mons, Belgium, 7000
        • Research Site
      • Roeselare, Belgium, 8800
        • Research Site
      • Yvoir, Belgium, 5530
        • Research Site
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Research Site
      • Sofia, Bulgaria, 1407
        • Research Site
      • Sofia, Bulgaria, 1330
        • Research Site
      • Varna, Bulgaria, 9010
        • Research Site
  • Canada
    • New Brunswick
      • Moncton, New Brunswick, Canada, E1C 6Z8
        • Research Site
      • Saint John, New Brunswick, Canada, E2L 4L2
        • Research Site
  • Chile
      • Santiago, Chile, 7500000
        • Research Site
      • Santiago, Chile, 8420383
        • Research Site
      • Temuco, Chile, 4810469
        • Research Site
  • Czechia
      • Nova Ves pod Plesi, Czechia, 262 04
        • Research Site
      • Praha 2, Czechia, 128 08
        • Research Site
      • Praha 5, Czechia, 150 06
        • Research Site
  • France
      • Avignon Cedex 9, France, 84918
        • Research Site
      • Bayonne, France, 64100
        • Research Site
      • Brest Cedex, France, 29609
        • Research Site
      • Creteil, France, 94010
        • Research Site
      • Le Mans, France, 72000
        • Research Site
      • Marseille Cedex 20, France, 13915
        • Research Site
      • Montpellier Cedex, France, 34295
        • Research Site
      • Nice, France, 06100
        • Research Site
      • Pau Cedex, France, 64046
        • Research Site
      • Saint Herblain, France, 44805
        • Research Site
      • Toulon, France, 83100
        • Research Site
      • Villejuif, France, 94800
        • Research Site
  • Germany
      • Berlin, Germany, 10117
        • Research Site
      • Berlin, Germany, 12351
        • Research Site
      • Berlin, Germany, 10967
        • Research Site
      • Dresden, Germany, 01307
        • Research Site
      • Gauting, Germany, 82131
        • Research Site
      • Halle, Germany, 06120
        • Research Site
      • Hamburg, Germany, 22081
        • Research Site
      • Hannover, Germany, 30625
        • Research Site
      • Homburg, Germany, 66421
        • Research Site
      • Köln, Germany, 51109
        • Research Site
      • Löwenstein, Germany, 74245
        • Research Site
      • Regensburg, Germany, 93053
        • Research Site
      • Trier, Germany, 54290
        • Research Site
      • Ulm, Germany, 89081
        • Research Site
      • Villingen-Schwenningen, Germany, 78052
        • Research Site
  • Greece
      • Athens, Greece, 11527
        • Research Site
      • Thessaloniki, Greece, 57010
        • Research Site
      • Thessaloniki, Greece, 54645
        • Research Site
  • Hong Kong
      • Hong Kong, Hong Kong
        • Research Site
  • Hungary
      • Miskolc, Hungary, 3529
        • Research Site
      • Törökbálint, Hungary, 2045
        • Research Site
      • Zalaegerszeg, Hungary, 8900
        • Research Site
      • Zalaegerszeg, Hungary, 8000
        • Research Site
  • Israel
      • Tel Hashomer, Israel, 52621
        • Research Site
  • Italy
      • Aviano, Italy, 33081
        • Research Site
      • Candiolo, Italy, 10060
        • Research Site
      • Catania, Italy, 95123
        • Research Site
      • Cremona, Italy, 26100
        • Research Site
      • Genova, Italy, 16100
        • Research Site
      • Lucca, Italy, 55100
        • Research Site
      • Milano, Italy, 20141
        • Research Site
      • Milano, Italy, 20132
        • Research Site
      • Milano, Italy, 20133
        • Research Site
      • Monza, Italy, 20900
        • Research Site
      • Napoli, Italy, 80131
        • Research Site
      • Orbassano, Italy, 10043
        • Research Site
      • Parma, Italy, 43100
        • Research Site
      • Pisa, Italy, 56124
        • Research Site
      • Rimini, Italy, 47900
        • Research Site
      • Terni, Italy, 05100
        • Research Site
  • Japan
      • Fukuoka-shi, Japan, 812-8582
        • Research Site
      • Habikino-shi, Japan, 583-8588
        • Research Site
      • Hidaka-shi, Japan, 350-1298
        • Research Site
      • Hirakata-shi, Japan, 573-1191
        • Research Site
      • Hirosaki-shi, Japan, 036-8545
        • Research Site
      • Hiroshima-shi, Japan, 730-8518
        • Research Site
      • Kanazawa, Japan, 920-8641
        • Research Site
      • Kobe-shi, Japan, 650-0047
        • Research Site
      • Kurume-shi, Japan, 830-0011
        • Research Site
      • Matsuyama-shi, Japan, 791-0280
        • Research Site
      • Nagoya-shi, Japan, 464-8681
        • Research Site
      • Nagoya-shi, Japan, 466-8560
        • Research Site
      • Nagoya-shi, Japan, 460-0001
        • Research Site
      • Natori-shi, Japan, 981-1293
        • Research Site
      • Okayama-shi, Japan, 700-8558
        • Research Site
      • Osaka-shi, Japan, 541-8567
        • Research Site
      • Osakasayama, Japan, 589-8511
        • Research Site
      • Sakai-shi, Japan, 591-8555
        • Research Site
      • Sapporo-shi, Japan, 003-0804
        • Research Site
      • Sapporo-shi, Japan, 060-8648
        • Research Site
      • Sendai-shi, Japan, 980-0873
        • Research Site
      • Shinjuku-ku, Japan, 162-8655
        • Research Site
      • Shinjuku-ku, Japan, 160-0023
        • Research Site
      • Sunto-gun, Japan, 411-8777
        • Research Site
      • Takatsuki-shi, Japan, 569-8686
        • Research Site
      • Wakayama-shi, Japan, 641-8510
        • Research Site
      • Yokohama-shi, Japan, 236-0024
        • Research Site
      • Yokohama-shi, Japan, 221-0855
        • Research Site
  • Korea, Republic of
      • Busan, Korea, Republic of, 49201
        • Research Site
      • Cheongju-si, Korea, Republic of, 28644
        • Research Site
      • Incheon, Korea, Republic of, 405-760
        • Research Site
      • Jeonnam, Korea, Republic of, 58128
        • Research Site
      • Seongnam-si, Korea, Republic of, 13620
        • Research Site
      • Seoul, Korea, Republic of, 05505
        • Research Site
      • Seoul, Korea, Republic of, 02841
        • Research Site
      • Seoul, Korea, Republic of, 06351
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Research Site
  • Poland
      • Lublin, Poland, 20-362
        • Research Site
      • Poznań, Poland, 60-569
        • Research Site
      • Warszawa, Poland, 02-781
        • Research Site
  • Romania
      • Alba Iulia, Romania, 510077
        • Research Site
      • Baia Mare, Romania, 430031
        • Research Site
      • Cluj Napoca, Romania, 400349
        • Research Site
      • Cluj-Napoca, Romania, 400132
        • Research Site
      • Onesti, Romania, 601048
        • Research Site
      • Oradea, Romania, 410469
        • Research Site
      • Timisoara, Romania, 300210
        • Research Site
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • Research Site
      • Omsk, Russian Federation, 644013
        • Research Site
      • Saint Petersburg, Russian Federation, 197758
        • Research Site
      • St. Petersburg, Russian Federation, 197022
        • Research Site
      • St. Petersburg, Russian Federation, 197758
        • Research Site
      • St. Petersburg, Russian Federation, 197002
        • Research Site
  • Serbia
      • Belgrad, Serbia, 11000
        • Research Site
      • Belgrade, Serbia, 11000
        • Research Site
      • Gornji Matejevac, Serbia, 18204
        • Research Site
      • Kragujevac, Serbia, 34000
        • Research Site
      • Sremska Kamenica, Serbia, 21204
        • Research Site
  • Singapore
      • Singapore, Singapore, 169610
        • Research Site
      • Singapore, Singapore, 308433
        • Research Site
      • Singapore, Singapore, 119074
        • Research Site
  • Spain
      • A Coruña, Spain, 15006
        • Research Site
      • Alicante, Spain, 03010
        • Research Site
      • Barcelona, Spain, 08003
        • Research Site
      • Barcelona, Spain, 08025
        • Research Site
      • Girona, Spain, 17007
        • Research Site
      • Jaén, Spain, 23007
        • Research Site
      • Lleida, Spain, 25198
        • Research Site
      • Madrid, Spain, 28046
        • Research Site
      • Madrid, Spain, 08035
        • Research Site
      • Madrid, Spain, 28050
        • Research Site
      • Madrid, Spain, 28007
        • Research Site
      • Madrid, Spain, 28033
        • Research Site
      • Madrid, Spain, 28005
        • Research Site
      • San Sebastian, Spain, 20014
        • Research Site
      • Sevilla, Spain, 41013
        • Research Site
      • Sevilla, Spain, 41071
        • Research Site
      • Valencia, Spain, 46026
        • Research Site
      • Valencia, Spain, 46014
        • Research Site
  • Taiwan
      • Taichung, Taiwan, 40705
        • Research Site
      • Taichung, Taiwan, 40447
        • Research Site
      • Tainan, Taiwan, 704
        • Research Site
      • Taipei, Taiwan, 235
        • Research Site
      • Taipei, Taiwan, 10002
        • Research Site
      • Taipei, Taiwan, 112
        • Research Site
      • Taipei, Taiwan, 116
        • Research Site
      • Taipei City, Taiwan, 110
        • Research Site
  • Thailand
      • Bangkok, Thailand, 10330
        • Research Site
      • Muang, Thailand, 50200
        • Research Site
      • Phitsanulok, Thailand, 65000
        • Research Site
      • Songkla, Thailand, 90110
        • Research Site
  • United Kingdom
      • Birmingham, United Kingdom, B15 2WB
        • Research Site
      • London, United Kingdom, EC1A 7BE
        • Research Site
      • London, United Kingdom, W1G 6AD
        • Research Site
      • Southampton, United Kingdom, SO16 6YD
        • Research Site
      • Stevenage, United Kingdom, SG1 4AB
        • Research Site
      • Truro, United Kingdom, TR1 3LJ
        • Research Site
      • Wolverhampton, United Kingdom, WV10 0QP
        • Research Site
  • United States
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Research Site
    • California
      • Anaheim, California, United States, 92801
        • Research Site
      • Duarte, California, United States, 91010
        • Research Site
      • La Jolla, California, United States, 92093
        • Research Site
      • San Diego, California, United States, 92123
        • Research Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Research Site
    • Florida
      • Fort Myers, Florida, United States, 33901
        • Research Site
      • Orlando, Florida, United States, 32804
        • Research Site
      • Port Saint Lucie, Florida, United States, 34952
        • Research Site
      • Saint Petersburg, Florida, United States, 33705
        • Research Site
    • Georgia
      • Athens, Georgia, United States, 30607
        • Research Site
      • Atlanta, Georgia, United States, 30322
        • Research Site
      • Lawrenceville, Georgia, United States, 30046
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Research Site
    • Iowa
      • Waterloo, Iowa, United States, 50701
        • Research Site
    • Kentucky
      • Ashland, Kentucky, United States, 41101
        • Research Site
    • Maryland
      • Rockville, Maryland, United States, 20850
        • Research Site
    • Michigan
      • Battle Creek, Michigan, United States, 49017
        • Research Site
    • Missouri
      • Saint Louis, Missouri, United States, 63156
        • Research Site
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
        • Research Site
    • New York
      • Bronx, New York, United States, 10461-2375
        • Research Site
      • Mineola, New York, United States, 11501
        • Research Site
      • New York, New York, United States, 10029
        • Research Site
      • New York, New York, United States, 10011
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Research Site
      • Pinehurst, North Carolina, United States, 28374
        • Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45242
        • Research Site
      • West Chester, Ohio, United States, 45069
        • Research Site
    • Tennessee
      • Chattanooga, Tennessee, United States, 37404
        • Research Site
      • Germantown, Tennessee, United States, 38138
        • Research Site
      • Nashville, Tennessee, United States, 37203
        • Research Site
    • Utah
      • Salt Lake City, Utah, United States, 84106
        • Research Site
    • Washington
      • Spokane, Washington, United States, 99208
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: MEDI4736 (durvalumab) monotherapy in Sub-study A
MEDI4736 (durvalumab) by intravenous infusion. Sub-study A for patients with PD-L1 positive tumors.
Drug: MEDI4736 (durvalumab)
MEDI4736 (durvalumab) treatment by intravenous infusion
Active Comparator: Standard of Care in Sub-study A
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study A for patients with PD-L1 positive tumors.
Drug: Vinorelbine
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.
Drug: Gemcitabine
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.
Drug: Erlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
Experimental: MEDI4736 (durvalumab) + tremelimumab in Sub-study B
MEDI4736 (durvalumab) by intravenous infusion and tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Drug: MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4)
MEDI4736 (durvalumab) in combination with tremelimumab (anti-CTLA4) treatment by intravenous infusion
Active Comparator: Standard of Care in Sub-study B
Investigator choice from Vinorelbine, Gemcitabine and Erlotinib. Sub-study B for patients with PD-L1 negative tumors.
Drug: Vinorelbine
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.
Drug: Gemcitabine
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.
Drug: Erlotinib
Erlotinib administered at a dose of 150 mg once daily as a tablet for oral administration
Experimental: MEDI4736 (durvalumab) monotherapy in Sub-study B
MEDI4736 (durvalumab) by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Drug: MEDI4736 (durvalumab)
MEDI4736 (durvalumab) treatment by intravenous infusion
Experimental: tremelimumab in Sub-study B
tremelimumab by intravenous infusion. Sub-study B for patients with PD-L1 negative tumors.
Drug: tremelimumab (anti-CTLA4)
tremelimumab (anti-CTLA4) treatment by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
From randomization (Day 1) until death due to any cause, approximately 36 months
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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
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
Percentage of Participants Alive at 12 Months (OS12)
Time Frame: From randomization (Day 1) up to 12 months
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.
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.
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
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.
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.
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.
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
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
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
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.
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
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Paul Stockman, MBChB, PhD, AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 13, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 9, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 28, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 28, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D4191C00004
  • 2014-000338-46 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing 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

IPD Sharing 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

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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