Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)
MYSTIC
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)(MYSTIC).
2 other identifiers
interventional
1,118
17 countries
196
Brief Summary
This is a randomized, open-label, multi-center, global, Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy and MEDI4736 monotherapy versus platinum-based SoC chemotherapy in the first-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type locally advanced or metastatic NSCLC
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2015
Longer than P75 for phase_3
196 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
First Submitted
Initial submission to the registry
May 20, 2015
CompletedFirst Posted
Study publicly available on registry
May 25, 2015
CompletedStudy Start
First participant enrolled
July 21, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 4, 2018
CompletedResults Posted
Study results publicly available
November 29, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2026
ExpectedMarch 2, 2026
January 1, 2026
3.2 years
May 20, 2015
October 4, 2019
February 10, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy
The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique.
From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy
The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments 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 withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary Outcomes (27)
OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
OS; PD-L1 (TC >=1%) Analysis Set Population
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
OS; FAS Population
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
PFS; PD-L1 (TC >=1%) Analysis Set Population
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
- +22 more secondary outcomes
Study Arms (3)
Monotherapy
EXPERIMENTALPD-L1 monoclonal Antibody monotherapy.
Combination Therapy
EXPERIMENTALPD-L1+Tremelimumab combination therapy
Standard of Care
ACTIVE COMPARATORStandard of Care chemotherapy treatment
Interventions
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Chemotherapy Agents
Eligibility Criteria
You may qualify if:
- Aged at least 18 years
- Documented evidence of Stage IV NSCLC
- No sensitizing EGFR mutation or ALK rearrangement
- No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC
- World Health Organization (WHO) Performance Status of 0 or 1
You may not qualify if:
- Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
- Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
- Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\]
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (196)
Research Site
Scottsdale, Arizona, 85259, United States
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Tucson, Arizona, 85715, United States
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Yuma, Arizona, 85364, United States
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Bakersfield, California, 93309, United States
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Fullerton, California, 92835, United States
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La Jolla, California, 92093, United States
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Los Angeles, California, 90024, United States
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Los Angeles, California, 90073, United States
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Redondo Beach, California, 90277, United States
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Sacramento, California, 95817, United States
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San Luis Obispo, California, 93401, United States
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Santa Maria, California, 93454, United States
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West Hollywood, California, 90048, United States
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New Haven, Connecticut, 06519, United States
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Jacksonville, Florida, 32256, United States
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Pembroke Pines, Florida, 33028, United States
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Tampa, Florida, 33612, United States
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Athens, Georgia, 30607, United States
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Honolulu, Hawaii, 96819, United States
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Baltimore, Maryland, 21231, United States
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Minneapolis, Minnesota, 55435, United States
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St Louis, Missouri, 63110, United States
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Omaha, Nebraska, 68198, United States
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Summit, New Jersey, 07901, United States
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Mineola, New York, 11501, United States
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New York, New York, 10016, United States
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New York, New York, 10021, United States
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New York, New York, 10032, United States
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Charlotte, North Carolina, 28204, United States
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Cleveland, Ohio, 44195, United States
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North Charleston, South Carolina, 29406, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Richmond, Virginia, 23298, United States
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Madison, Wisconsin, 53705, United States
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Box Hill, 3128, Australia
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Gosford, 2250, Australia
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Kogarah, 2217, Australia
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Melbourne, 3000, Australia
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Port Macquarie, 2444, Australia
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Southport, 4215, Australia
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St Leonards, 2065, Australia
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Brussels, 1090, Belgium
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Charleroi, 6000, Belgium
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Duffel, 2570, Belgium
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Leuven, 3000, Belgium
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Liège, 4000, Belgium
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Greater Sudbury, Ontario, P3E 5J1, Canada
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Kingston, Ontario, K7L 2V7, Canada
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Newmarket, Ontario, L3Y 2P9, Canada
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Oshawa, Ontario, L1G 2B9, Canada
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Saint Catherines, Ontario, L2R 6P9, Canada
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Sault Ste. Marie, Ontario, P6A 0A8, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Regina, Saskatchewan, S4T 7T1, Canada
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Saskatoon, Saskatchewan, S7N 4H4, Canada
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Bordeaux, 33000, France
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Brest, 29609, France
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Créteil, 94010, France
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Lille, 59000, France
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Lyon, 69373, France
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Marseille, 13915, France
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Aachen, 52074, Germany
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Bad Berka, 99437, Germany
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Berlin, 10967, Germany
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Berlin, 12351, Germany
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Freiburg im Breisgau, 79106, Germany
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Gauting, 82131, Germany
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Hamburg, 20251, Germany
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Heidelberg, 69126, Germany
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Hemer, 58675, Germany
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Homburg/Saar, 66421, Germany
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Immenhausen, 34376, Germany
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Löwenstein, 74245, Germany
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Lübeck, 23538, Germany
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Mainz, 55131, Germany
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Münster, 48149, Germany
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Oldenburg, 26121, Germany
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Ulm, 89081, Germany
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Velbert, 42551, Germany
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Würzburg, 97080, Germany
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Budapest, 1121, Hungary
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Deszk, 6772, Hungary
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Edelény, 3780, Hungary
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Kaposvár, 7400, Hungary
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Kecskemét, 6000, Hungary
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Miskolc, 3529, Hungary
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Nyíregyháza, 4400, Hungary
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Pécs, 7624, Hungary
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Székesfehérvár, 8000, Hungary
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Genova, 16100, Italy
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Meldola, 47014, 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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San Giovanni Rotondo, 71013, Italy
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Siena, 53100, Italy
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Fukushima, 960-1295, Japan
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Himeji-shi, 670-8520, Japan
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Hirakata-shi, 573-1191, Japan
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Hirosaki-shi, 036-8545, Japan
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Iizuka-shi, 820-8505, Japan
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Iwakuni-shi, 740-8510, Japan
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Izumi-shi, 594-0073, Japan
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Kanazawa, 920-8641, Japan
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Kishiwada-shi, 596-8501, Japan
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Kobe, 650-0047, Japan
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Koga-shi, 811-3195, Japan
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Kyoto, 607-8062, Japan
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Kyoto, 615-8256, Japan
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Mitaka-shi, 181-8611, Japan
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Nagaoka-shi, 940-2085, Japan
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Nagoya, 460-0001, Japan
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Nagoya, 466-8560, Japan
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Okayama, 700-8607, Japan
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Osaka, 541-8567, Japan
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Osaka, 543-0035, Japan
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Saga, 840-8571, Japan
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Saitama-shi, 336-8522, Japan
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Sakaishi, 591-8555, Japan
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Sayama, 589-8511, Japan
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Sendai, 980-0873, Japan
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Shinjuku-ku, 162-8655, Japan
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Tokushima, 770-8503, Japan
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Ube-shi, 755-0241, Japan
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Yokohama, 232-0024, Japan
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Yokohama, 241-8515, Japan
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Yokosuka-shi, 238-8558, Japan
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's-Hertogenbosch, 5223 GZ, Netherlands
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Amsterdam, 1066 CX, Netherlands
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Arnhem, 6815 AD, Netherlands
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Breda, 4818 CK, Netherlands
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Groningen, 9713 GZ, Netherlands
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Maastricht, 6202 AZ, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Moscow, 105229, Russia
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Moscow, 111123, Russia
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Moscow, 115478, Russia
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Moscow, 125315, Russia
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Moscow, 143423, Russia
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Obninsk, 249036, Russia
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Omsk, 644013, Russia
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Saint Petersburg, 194291, Russia
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Saint Petersburg, 197022, Russia
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Saint Petersburg, 197758, Russia
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Busan, 47392, South Korea
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Changwon-si, 51353, South Korea
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Cheongju-si, 28644, South Korea
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Daegu, 42415, South Korea
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Daegu, 42601, South Korea
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Daejeon, 35015, South Korea
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Goyang-si, 10408, South Korea
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Incheon, 21565, South Korea
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Jinju, 660-702, South Korea
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Seongnam-si, 13620, South Korea
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Seongnam-si, 463-712, South Korea
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Seoul, 03181, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Seoul, 134-791, South Korea
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Seoul, 135-710, South Korea
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Seoul, 156-707, South Korea
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Suwon, 16499, South Korea
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Ulsan, 44033, South Korea
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A Coruña, 15006, Spain
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Alicante, 03010, Spain
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Barcelona, 08035, Spain
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Barcelona, 08036, Spain
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Girona, 17007, Spain
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Jaén, 23007, Spain
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León, 24071, Spain
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Madrid, 28005, Spain
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Madrid, 28040, Spain
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Madrid, 28046, Spain
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Majadahonda, 28222, Spain
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Málaga, 29010, Spain
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Seville, 41009, Spain
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Seville, 41013, Spain
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Valencia, 46026, Spain
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Bellinzona, CH-6500, Switzerland
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Lausanne, 1011, Switzerland
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Kaohsiung City, 82445, Taiwan
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Kaohsiung City, 83301, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Taipei, 112, Taiwan
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Taipei, 235, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10330, Thailand
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Chiang Mai, 50200, Thailand
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Hat Yai, 90110, Thailand
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Khon Kaen, 40002, Thailand
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Hanoi, 100000, Vietnam
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Hanoi, 10000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
Related Publications (2)
Garon EB, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, Robinet G, Le Moulec S, Natale R, Schneider J, Shepherd FA, Garassino MC, Geater SL, Szekely ZP, Van Ngoc T, Liu F, Scheuring U, Patel N, Peters S, Rizvi NA. Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC). Clin Lung Cancer. 2021 Jul;22(4):301-312.e8. doi: 10.1016/j.cllc.2021.02.010. Epub 2021 Feb 19.
PMID: 33775558DERIVEDRizvi NA, Cho BC, Reinmuth N, Lee KH, Luft A, Ahn MJ, van den Heuvel MM, Cobo M, Vicente D, Smolin A, Moiseyenko V, Antonia SJ, Le Moulec S, Robinet G, Natale R, Schneider J, Shepherd FA, Geater SL, Garon EB, Kim ES, Goldberg SB, Nakagawa K, Raja R, Higgs BW, Boothman AM, Zhao L, Scheuring U, Stockman PK, Chand VK, Peters S; MYSTIC Investigators. Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 May 1;6(5):661-674. doi: 10.1001/jamaoncol.2020.0237.
PMID: 32271377DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- STUDY DIRECTOR
Stuart McIntosh, MD
AstraZeneca, Alderley Park, Cheshire, UK
- PRINCIPAL INVESTIGATOR
Naiyer Rizvi, MD
Columbia University Medical Center, New York, NY, USA
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
May 20, 2015
First Posted
May 25, 2015
Study Start
July 21, 2015
Primary Completion
October 4, 2018
Study Completion (Estimated)
December 31, 2026
Last Updated
March 2, 2026
Results First Posted
November 29, 2019
Record last verified: 2026-01
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.