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).

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

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small-Cell Lung Carcinoma NSCLC
• Intervention / Treatment: Biological: MEDI4736 (Durvalumab); Biological: MEDI4736 (Durvalumab)+Tremelimumab; Biological: Tremelimumab; Drug: Paclitaxel + Carboplatin; Drug: Gemcitabine + Cisplatin; Drug: Gemcitabine + Carboplatin; Drug: Pemetrexed + Cisplatin; Drug: Pemetrexed + Carboplatin

Detailed Description

Patients will be randomized in a 1:1:1 ratio to receive treatment with MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy, or Standard of Care (SoC) therapy.

• Study Type: Interventional
• Enrollment (Actual): 1118
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Research Site
  • Gosford, Australia, 2250
    • Research Site
  • Kogarah, Australia, 2217
    • Research Site
  • Melbourne, Australia, 3000
    • Research Site
  • Port Macquarie, Australia, 2444
    • Research Site
  • Southport, Australia, 4215
    • Research Site
  • St Leonards, Australia, 2065
    • Research Site
• Belgium
  • Brussels, Belgium, 1090
    • Research Site
  • Charleroi, Belgium, 6000
    • Research Site
  • Duffel, Belgium, 2570
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
  • Liège, Belgium, 4000
    • Research Site
• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Research Site
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Research Site
    • Oshawa, Ontario, Canada, L1G 2B9
      • Research Site
    • Sault Ste. Marie, Ontario, Canada, P6A 0A8
      • Research Site
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Research Site
    • Sudbury, Ontario, Canada, P3E 5J1
      • Research Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Research Site
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Research Site
• France
  • Bordeaux Cedex, France, 33000
    • Research Site
  • Brest Cedex, France, 29609
    • Research Site
  • Creteil, France, 94010
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  • Lille, France, 59000
    • Research Site
  • Lyon Cedex 08, France, 69373
    • Research Site
  • Marseille cedex, France, 13915
    • Research Site
• Germany
  • Aachen, Germany, 52074
    • Research Site
  • Bad Berka, Germany, 99437
    • Research Site
  • Berlin, Germany, 12351
    • Research Site
  • Berlin, Germany, 10967
    • Research Site
  • Freiburg, Germany, 79106
    • Research Site
  • Gauting, Germany, 82131
    • Research Site
  • Hamburg, Germany, 20251
    • Research Site
  • Heidelberg, Germany, 69126
    • Research Site
  • Hemer, Germany, 58675
    • Research Site
  • Homburg/Saar, Germany, 66421
    • Research Site
  • Immenhausen, Germany, 34376
    • Research Site
  • Lubeck, Germany, 23538
    • Research Site
  • Löwenstein, Germany, 74245
    • Research Site
  • Mainz, Germany, 55131
    • Research Site
  • Münster, Germany, 48149
    • Research Site
  • Oldenburg, Germany, 26121
    • Research Site
  • Ulm, Germany, 89081
    • Research Site
  • Velbert, Germany, 42551
    • Research Site
  • Würzburg, Germany, 97080
    • Research Site
• Hungary
  • Budapest, Hungary, 1121
    • Research Site
  • Deszk, Hungary, 6772
    • Research Site
  • Edelény, Hungary, 3780
    • Research Site
  • Kaposvár, Hungary, 7400
    • Research Site
  • Kecskemét, Hungary, 6000
    • Research Site
  • Miskolc, Hungary, 3529
    • Research Site
  • Nyíregyháza, Hungary, 4400
    • Research Site
  • Pécs, Hungary, 7624
    • Research Site
  • Székesfehérvár, Hungary, 8000
    • Research Site
• Italy
  • Genova, Italy, 16100
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Milano, Italy, 20141
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  • Milano, Italy, 20132
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  • Milano, Italy, 20133
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  • San Giovanni Rotondo, Italy, 71013
    • Research Site
  • Siena, Italy, 53100
    • Research Site
• Japan
  • Fukushima-shi, Japan, 960-1295
    • Research Site
  • Himeji-shi, Japan, 670-8520
    • Research Site
  • Hirakata-shi, Japan, 573-1191
    • Research Site
  • Hirosaki-shi, Japan, 036-8545
    • Research Site
  • Iizuka-shi, Japan, 820-8505
    • Research Site
  • Iwakuni-shi, Japan, 740-8510
    • Research Site
  • Izumi-shi, Japan, 594-0073
    • Research Site
  • Kanazawa, Japan, 920-8641
    • Research Site
  • Kishiwada-shi, Japan, 596-8501
    • Research Site
  • Kobe-shi, Japan, 650-0047
    • Research Site
  • Koga-shi, Japan, 811-3195
    • Research Site
  • Kyoto-shi, Japan, 607-8062
    • Research Site
  • Kyoto-shi, Japan, 615-8256
    • Research Site
  • Mitaka-shi, Japan, 181-8611
    • Research Site
  • Nagaoka-shi, Japan, 940-2085
    • Research Site
  • Nagoya-shi, Japan, 466-8560
    • Research Site
  • Nagoya-shi, Japan, 460-0001
    • Research Site
  • Okayama-shi, Japan, 700-8607
    • Research Site
  • Osaka-shi, Japan, 541-8567
    • Research Site
  • Osaka-shi, Japan, 543-0035
    • Research Site
  • Osakasayama, Japan, 589-8511
    • Research Site
  • Saga-shi, Japan, 840-8571
    • Research Site
  • Saitama-shi, Japan, 336-8522
    • Research Site
  • Sakai-shi, Japan, 591-8555
    • Research Site
  • Sendai-shi, Japan, 980-0873
    • Research Site
  • Shinjuku-ku, Japan, 162-8655
    • Research Site
  • Tokushima-shi, Japan, 770-8503
    • Research Site
  • Ube-shi, Japan, 755-0241
    • Research Site
  • Yokohama-shi, Japan, 241-8515
    • Research Site
  • Yokohama-shi, Japan, 236-0024
    • Research Site
  • Yokosuka-shi, Japan, 238-8558
    • Research Site
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Research Site
  • Changwon-si, Korea, Republic of, 51353
    • Research Site
  • Cheongju-si, Korea, Republic of, 28644
    • Research Site
  • Daegu, Korea, Republic of, 42601
    • Research Site
  • Daegu, Korea, Republic of, 42415
    • Research Site
  • Daejeon, Korea, Republic of, 35015
    • Research Site
  • Goyang-si, Korea, Republic of, 10408
    • Research Site
  • Incheon, Korea, Republic of, 21565
    • Research Site
  • Jinju-si, Korea, Republic of, 660-702
    • Research Site
  • Seongnam-Si, Korea, Republic of, 463-712
    • Research Site
  • Seongnam-si, Korea, Republic of, 13620
    • Research Site
  • Seoul, Korea, Republic of, 03722
    • Research Site
  • Seoul, Korea, Republic of, 05505
    • Research Site
  • Seoul, Korea, Republic of, 135-710
    • Research Site
  • Seoul, Korea, Republic of, 03181
    • Research Site
  • Seoul, Korea, Republic of, 156-707
    • Research Site
  • Seoul, Korea, Republic of, 134-791
    • Research Site
  • Suwon-si, Korea, Republic of, 16499
    • Research Site
  • Ulsan, Korea, Republic of, 44033
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Research Site
  • Arnhem, Netherlands, 6815 AD
    • Research Site
  • Breda, Netherlands, 4818 CK
    • Research Site
  • Den Bosch, Netherlands, 5223 GZ
    • Research Site
  • Groningen, Netherlands, 9713 GZ
    • Research Site
  • Maastricht, Netherlands, 6202 AZ
    • Research Site
  • Rotterdam, Netherlands, 3015 GD
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Research Site
  • Moscow, Russian Federation, 125315
    • Research Site
  • Moscow, Russian Federation, 111123
    • Research Site
  • Moscow, Russian Federation, 143423
    • Research Site
  • Moscow, Russian Federation, 105229
    • Research Site
  • Obninsk, Russian Federation, 249036
    • Research Site
  • Omsk, Russian Federation, 644013
    • Research Site
  • Saint Petersburg, Russian Federation, 197022
    • Research Site
  • Saint-Petersburg, Russian Federation, 194291
    • Research Site
  • St. Petersburg, Russian Federation, 197022
    • Research Site
  • St. Petersburg, Russian Federation, 197758
    • Research Site
• Spain
  • A Coruña, Spain, 15006
    • Research Site
  • Alicante, Spain, 03010
    • Research Site
  • Barcelona, Spain, 08035
    • Research Site
  • Barcelona, Spain, 08036
    • Research Site
  • Gerona, Spain, 17007
    • Research Site
  • Jaén, Spain, 23007
    • Research Site
  • León, Spain, 24071
    • Research Site
  • Madrid, Spain, 28046
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28005
    • Research Site
  • Majadahonda, Spain, 28222
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Sevilla, Spain, 41009
    • Research Site
  • Sevilla, Spain, 41013
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
• Switzerland
  • Bellinzona, Switzerland, CH-6500
    • Research Site
  • Lausanne, Switzerland, 1011
    • Research Site
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • Research Site
  • Kaohsiung, Taiwan, 83301
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Tainan City, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 235
    • Research Site
  • Taipei, Taiwan, 112
    • Research Site
  • Tao-Yuan, Taiwan, 333
    • Research Site
• Thailand
  • Bangkok, Thailand, 10330
    • Research Site
  • Chiang Mai, Thailand, 50200
    • Research Site
  • Hat Yai, Thailand, 90110
    • Research Site
  • Khon Kaen, Thailand, 40002
    • Research Site
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Research Site
    • Tucson, Arizona, United States, 85715
      • Research Site
    • Yuma, Arizona, United States, 85364
      • Research Site
  • California
    • Bakersfield, California, United States, 93309
      • Research Site
    • Fullerton, California, United States, 92835
      • Research Site
    • La Jolla, California, United States, 92093
      • Research Site
    • Los Angeles, California, United States, 90073
      • Research Site
    • Los Angeles, California, United States, 90024
      • Research Site
    • Redondo Beach, California, United States, 90277
      • Research Site
    • Sacramento, California, United States, 95817
      • Research Site
    • San Luis Obispo, California, United States, 93401
      • Research Site
    • Santa Maria, California, United States, 93454
      • Research Site
    • West Hollywood, California, United States, 90048
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Research Site
    • Pembroke Pines, Florida, United States, 33028
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
  • Georgia
    • Athens, Georgia, United States, 30607
      • Research Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96819
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55435
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Research Site
  • New Jersey
    • Summit, New Jersey, United States, 07901
      • Research Site
  • New York
    • Mineola, New York, United States, 11501
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
    • New York, New York, United States, 10021
      • Research Site
    • New York, New York, United States, 10032
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Research Site
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Research Site
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Research Site
    • Nashville, Tennessee, United States, 37232
      • Research Site
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • Research Site
• Vietnam
  • Hanoi, Vietnam, 100000
    • Research Site
  • Hanoi, Vietnam, 10000
    • Research Site
  • Hanoi City, Vietnam, 100000
    • Research Site
  • Ho Chi Minh, Vietnam, 700000
    • Research Site
  • Ho Chi Minh, Vietnam, 70000
    • Research Site
  • Ho Chi Minh city, Vietnam, 700000
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

• 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

Exclusion Criteria:

Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
2. Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
3. 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
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease]

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; Standard of Care chemotherapy treatment	Drug: Paclitaxel + Carboplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Gemcitabine + Cisplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Gemcitabine + Carboplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Pemetrexed + Cisplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy; Drug: Pemetrexed + Carboplatin; Chemotherapy Agents; Other Names: Platinum based Standard of Care Chemotherapy
Experimental: Monotherapy; PD-L1 monoclonal Antibody monotherapy.	Biological: MEDI4736 (Durvalumab)
Experimental: Combination Therapy; PD-L1+Tremelimumab combination therapy	Biological: MEDI4736 (Durvalumab)+Tremelimumab; Biological: Tremelimumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy	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 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	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 until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
OS; FAS Population	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 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	The PFS per RECIST 1.1 using 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). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 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).
PFS; PD-L1 (TC >=1%) Analysis Set Population	The PFS per RECIST 1.1 using 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). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 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).
PFS; FAS Population	The PFS per RECIST 1.1 using 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). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 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).
Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
ORR; PD-L1 (TC >=1%) Analysis Set Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
ORR; FAS Population	The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population	The DoR per RECIST 1.1 using BICR assessments 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 (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
DoR; PD-L1 (TC >=1%) Analysis Set Population	The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
DoR; FAS Population	The DoR per RECIST 1.1 using BICR assessments 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 (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs 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 TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met).	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).
Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Percentage of Participants APF12; FAS Population	The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique.	Tumour scans performed at baseline then every 6 weeks up to 12 months.
Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
PFS2; PD-L1 (TC >=1%) Analysis Set Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
PFS2; FAS Population	The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death.	Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months	Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items with higher scores representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change is defined as an absolute change in the score from baseline of >=10.	At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.
Serum Concentrations of Durvalumab	Blood samples were collected to determine the serum concentration of durvalumab.	Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.
Serum Concentrations of Tremelimumab	Blood samples were collected to determine the serum concentration of tremelimumab.	Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.
Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab	Blood samples were collected to determine the Cmax_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Within 1 hour after end of infusion on infusion day at Week 12.
Cmax_ss of Tremelimumab	Blood samples were collected to determine the Cmax_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Within 1 hour after end of infusion on infusion day at Week 12.
Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab	Blood samples were collected to determine the Ctrough_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Pre-dose at Week 12.
Ctrough_ss of Tremelimumab	Blood samples were collected to determine the Ctrough_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods.	Pre-dose at Week 12.
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab	Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
Number of Participants With ADA Response to Tremelimumab	Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.	At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Stuart McIntosh, MD, AstraZeneca, Alderley Park, Cheshire, UK; Principal Investigator: Naiyer Rizvi, MD, Columbia University Medical Center, New York, NY, USA

Publications and helpful links

General Publications

• 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.
• Rizvi 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. Erratum In: JAMA Oncol. 2020 Nov 1;6(11):1815.

Helpful Links

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Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2015
• Primary Completion (Actual): October 4, 2018
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: May 20, 2015
• First Submitted That Met QC Criteria: May 22, 2015
• First Posted (Estimated): May 25, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 16, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC, PD-L1, MEDI4736, Tremelimumab, PFS, OS
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Cisplatin; Durvalumab; Tremelimumab; Antibodies, Monoclonal; Pemetrexed; Gemcitabine
• Other Study ID Numbers: D419AC00001; 2015-001279-39 (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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No