Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Concurrent Chemoradiation Therapy (ADRIATIC)

This is a Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center, International Study of Durvalumab or Durvalumab and Tremelimumab as Consolidation Treatment for Patients with LS-SCLC Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Durvalumab; Other: Placebo; Drug: Tremelimumab

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • CABA, Argentina, C1012AAR
    • Research Site
  • Ciudad de Buenos Aires, Argentina, C1280AEB
    • Research Site
  • Córdoba, Argentina, X5004BAL
    • Research Site
  • Mar del Plata, Argentina, 7600
    • Research Site
  • Rosario, Argentina, 2000
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• Belgium
  • Aalst, Belgium, 9300
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  • Anderlecht, Belgium, 1070
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  • Brussels, Belgium, 1200
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  • Hasselt, Belgium, 3500
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  • Roeselare, Belgium, 8800
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• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
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  • CA
    • Toronto, CA, Canada, M5G 2M9
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  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
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  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
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    • London, Ontario, Canada, N6A 5W9
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    • Ottawa, Ontario, Canada, K1H 8L6
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    • Toronto, Ontario, Canada, M4N 3M5
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  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
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• China
  • Beijing, China, 100142
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  • Beijing, China, 100021
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  • Beijing, China, 100730
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  • Beijing, China, 100191
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  • Beijing, China, 100036
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  • Bengbu, China, 233004
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  • Changchun, China, 130000
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  • Changsha, China, 410013
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  • Chengdu, China, 610042
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  • Chongqing, China, 400030
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  • Chongqing, China, 400042
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  • Fuzhou, China, 350011
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  • Hangzhou, China, 310003
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  • Hefei, China, 230601
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  • Shanghai, China, 200032
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  • Shanghai, China, 200030
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  • Shenyang, China, 110001
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  • Shenyang, China, 110042
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  • Tianjin, China, 300060
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  • Wuhan, China, 430022
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  • Wuhan, China, 430030
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  • Wuhan, China, 430010
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  • Yangzhou, China, 225001
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  • Zhengzhou, China, 450008
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• Czechia
  • Brno, Czechia, 639 00
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  • Olomouc, Czechia, 77900
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  • Ostrava, Czechia, 703 00
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  • Prague, Czechia, 128 08
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  • Prague, Czechia, 140 59
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• Germany
  • Berlin, Germany, 12351
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  • Cologne, Germany, 51109
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  • Freiburg im Breisgau, Germany, 79106
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  • Gauting, Germany, 82131
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  • Heidelberg, Germany, 69126
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  • Mainz, Germany, 55131
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  • Münster, Germany, 48149
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  • Oldenburg, Germany, 26121
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  • Regensburg, Germany, 93053
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  • Stuttgart, Germany, 70376
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  • Würzburg, Germany, 97080
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• India
  • Bengaluru, India, 560076
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  • Gurgaon, India, 122001
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• Italy
  • Brescia, Italy, 25123
    • Research Site
  • Milan, Italy, 20141
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  • Milan, Italy, 20133
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  • Orbassano, Italy, 10043
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  • Parma, Italy, 43126
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  • Roma, Italy, 00100
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  • Rozzano, Italy, 20089
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  • Terni, Italy, 05100
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• Japan
  • Bunkyō City, Japan, 160-0023
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  • Chūōku, Japan, 104-0045
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  • Fukuoka, Japan, 812-8582
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  • Iwakuni-shi, Japan, 740-8510
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  • Kashiwa, Japan, 277-8577
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  • Kurume-shi, Japan, 830-0011
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  • Kōtoku, Japan, 135-8550
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  • Nagoya, Japan, 466-8560
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  • Nagoya, Japan, 464-8681
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  • Niigata, Japan, 951-8566
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  • Sakaishi, Japan, 591-8555
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  • Sapporo, Japan, 003-0804
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  • Sayama, Japan, 589-8511
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  • Sendai, Japan, 980-0873
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  • Sunto-gun, Japan, 411-8777
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  • Tokushima, Japan, 770-8503
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  • Ube-shi, Japan, 755-0241
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• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223 GZ
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  • Amsterdam, Netherlands, 1081 HV
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  • Groningen, Netherlands, 9713 GZ
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  • Harderwijk, Netherlands, 3844 DG
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  • Hengelo, Netherlands, 7555 DL
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• Poland
  • Gdansk, Poland, 80-952
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  • Olsztyn, Poland, 10-357
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  • Poznan, Poland, 60-569
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  • Tomaszów Mazowiecki, Poland, 97-200
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  • Warsaw, Poland, 02-781
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  • Wroclaw, Poland, 53-413
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• Russia
  • Kazan', Russia, 420029
    • Research Site
  • Kirov, Russia, 610021
    • Research Site
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 105229
    • Research Site
  • Moscow, Russia, 125284
    • Research Site
  • Obninsk, Russia, 249036
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  • Omsk, Russia, 644013
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  • Ufa, Russia, 450054
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  • Volgograd, Russia, 400138
    • Research Site
• South Korea
  • Changwon-si, South Korea, 51353
    • Research Site
  • Cheongju-si, South Korea, 28644
    • Research Site
  • Daegu, South Korea, 42415
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  • Goyang-si, South Korea, 10408
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  • Jinju, South Korea, 52727
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  • Seongnam-si, South Korea, 13620
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  • Seoul, South Korea, 03080
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  • Seoul, South Korea, 03722
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  • Seoul, South Korea, 05505
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  • Suwon, South Korea, 16499
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• Spain
  • Barcelona, Spain, 08035
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  • Barcelona, Spain, 08003
    • Research Site
  • Madrid, Spain, 28034
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  • Madrid, Spain, 28041
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  • Madrid, Spain, 28040
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  • Oviedo, Spain, 33011
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  • Seville, Spain, 41013
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  • Valencia, Spain, 46026
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  • Zaragoza, Spain, 50009
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• Taiwan
  • Hsinchu, Taiwan, 300
    • Research Site
  • Kaohsiung City, Taiwan, 83301
    • Research Site
  • Keelung, Taiwan, 20445
    • Research Site
  • Taichung, Taiwan, 40705
    • Research Site
  • Tainan, Taiwan, 736
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 235
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  • Taipei, Taiwan, 112
    • Research Site
  • Taoyuan, Taiwan, 333
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  • Yunlin, Taiwan, 640
    • Research Site
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01060
    • Research Site
  • Ankara, Turkey (Türkiye), 06230
    • Research Site
  • Ankara, Turkey (Türkiye), 06280
    • Research Site
  • Antalya, Turkey (Türkiye), 07059
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  • Edirne, Turkey (Türkiye), 22030
    • Research Site
  • Istanbul, Turkey (Türkiye), 34030
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  • Izmir, Turkey (Türkiye), 35620
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  • Konya, Turkey (Türkiye), 42080
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  • Samsun, Turkey (Türkiye)
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• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Truro, United Kingdom, TR1 3LJ
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• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Research Site
  • California
    • Santa Rosa, California, United States, 95403
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  • Connecticut
    • New Haven, Connecticut, United States, 06510
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  • Florida
    • Fort Myers, Florida, United States, 33901
      • Research Site
    • Orange City, Florida, United States, 32763
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    • St. Petersburg, Florida, United States, 33705
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  • Georgia
    • Marietta, Georgia, United States, 30060
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  • Illinois
    • Hines, Illinois, United States, 60141
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  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Research Site
    • Muncie, Indiana, United States, 47303
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  • Kentucky
    • Lexington, Kentucky, United States, 40536
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  • Maryland
    • Annapolis, Maryland, United States, 21401
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    • Baltimore, Maryland, United States, 21287
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    • Towson, Maryland, United States, 21204
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  • Massachusetts
    • Boston, Massachusetts, United States, 02114
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  • Michigan
    • Detroit, Michigan, United States, 48201
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    • Grand Rapids, Michigan, United States, 49503
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  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
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  • New Jersey
    • Summit, New Jersey, United States, 07902
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  • New York
    • New Hyde Park, New York, United States, 11042
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  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
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  • Oregon
    • Portland, Oregon, United States, 97239
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  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
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    • Pittsburgh, Pennsylvania, United States, 15212
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  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
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  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
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    • Nashville, Tennessee, United States, 37203
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    • Nashville, Tennessee, United States, 37232
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  • Texas
    • Dallas, Texas, United States, 75390
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  • Washington
    • Kennewick, Washington, United States, 99336
      • Research Site
    • Tacoma, Washington, United States, 98405
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  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • Research Site
    • Huntington, West Virginia, United States, 25701
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  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
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• Vietnam
  • Hanoi, Vietnam, 100000
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  • Ho Chi Minh City, Vietnam, 700000
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  • Ho Chi Minh City, Vietnam, 70000
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  • Hà Nội, Vietnam, 100000
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Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III).
2. Received 4 cycles of chemotherapy concurrent with radiotherapy, which must be completed within 1 to 42 days prior to randomization and the first dose of IP. Chemotherapy must contain platinum and IV etoposide. Radiotherapy must be either total 60-66 Gy over 6 weeks for the standard QD regimen or total 45 Gy over 3 weeks for hyperfractionated BD schedules.
3. PCI may be delivered at the discretion of investigator and local standard of care, and must be conducted after the end of cCRT and completed between 1 to 42 days to first dose of IP.

4 .Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.

Exclusion criteria:

1. Extensive-stage SCLC
2. Active or prior documented autoimmune or inflammatory disorders
3. Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
4. Active infection including tuberculosis, HIV, hepatitis B and C
5. Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab + Placebo; Durvalumab monotherapy: Durvalumab (1500 mg intravenous [IV]) q4w in combination with placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with placebo saline solution.	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Other: Placebo; Placebo IV (intravenous infusion)
Experimental: Durvalumab + Tremelimumab; Durvalumab in combination with tremelimumab: Durvalumab (1500 mg IV) q4w in combination with tremelimumab (75 mg IV) q4w for up to 4 doses/cycles each, followed by durvalumab 1500 mg q4w. The first durvalumab monotherapy 1500 mg dose q4w will be 4 weeks after the final dose of durvalumab in combination with tremelimumab.	Drug: Durvalumab; Durvalumab IV (intravenous infusion); Other Names: MEDI4736; Drug: Tremelimumab; Tremelimumab IV (intravenous infusion)
Placebo Comparator: Placebo + Placebo; Placebo: Placebo saline solution (IV) q4w in combination with a second placebo saline solution (IV) q4w for up to 4 doses/cycles each, followed by a single placebo saline solution q4w. The first placebo saline solution monotherapy dose q4w will be 4 weeks after the final dose of the 2 placebo saline solutions in combination.	Other: Placebo; Placebo IV (intravenous infusion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durvalumab Versus Placebo: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective disease progression (PD) or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.	Response evaluations performed every 8 weeks (q8w) ± 1 week up to 72 weeks, then every 12 weeks (q12w) ± 1 week up to 96 weeks, and then every 24 weeks (q24w) thereafter until PD, up to DCO date 15 January 2024 (a maximum of approximately 1936 days)
Durvalumab Versus Placebo: Overall Survival (OS)	OS was defined as the time from the date of randomization until death due to any cause. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.	From date of randomization until death due to any cause, up to DCO date 15 January 2024 (a maximum of approximately 1936 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durvalumab Plus Tremelimumab Combination Versus Placebo: Progression-Free Survival Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.	Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months
Durvalumab Plus Tremelimumab Combination Versus Placebo: Overall Survival	OS is defined as the time from the date of randomization until death due to any cause.	From date of randomization until death due to any cause, up to approximately 89 months
Durvalumab Versus Placebo: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	ORR per RECIST 1.1 assessed by BICR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) (i.e., unconfirmed response). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to DCO date 15 January 2024 (a maximum of approximately 1936 days)
Durvalumab Plus Tremelimumab Combination Versus Placebo: Objective Response Rate Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	ORR per RECIST 1.1 assessed by BICR is defined as the percentage of participants with at least 1 visit response of CR or PR (i.e., unconfirmed response). CR is defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	From date of randomization until death due to any cause, up to approximately 89 months
Durvalumab Versus Placebo: Percentage of Participants Progression-Free at 18 Months Following Randomization (PFS18) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS18 was defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 18 months following randomization.	Month 18
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Progression-Free at 18 Months Following Randomization Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS18 is defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 18 months following randomization.	Month 18
Durvalumab Versus Placebo: Percentage of Participants Progression-Free at 24 Months Following Randomization (PFS24) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS24 was defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 24 months following randomization.	Month 24
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Progression-Free at 24 Months Following Randomization Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this included the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir. The PFS24 is defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by BICR at 24 months following randomization.	Month 24
Durvalumab Plus Tremelimumab Combination Versus Placebo: Time to Death or Distant Metastasis (TTDM) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	TTDM per RECIST 1.1 is defined as the time from the date of randomization until the first date of distant metastasis or death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the radiation field according to RECIST 1.1 or proven by biopsy.	Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months
Durvalumab Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization (OS24)	OS was defined as the time from the date of randomization until death due to any cause. The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months after randomization.	Month 24
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization	OS is defined as the time from the date of randomization until death due to any cause. The OS24 is defined as the Kaplan-Meier estimate of OS at 24 months after randomization.	Month 24
Durvalumab Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization (OS36)	OS was defined as the time from the date of randomization until death due to any cause. The OS36 was defined as the Kaplan-Meier estimate of OS at 36 months after randomization.	Month 36
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization	OS is defined as the time from the date of randomization until death due to any cause. The OS36 is defined as the Kaplan-Meier estimate of OS at 36 months after randomization.	Month 36
Durvalumab Plus Tremelimumab Combination Versus Placebo: Time From Randomization to Second Progression (PFS2)	PFS2 is defined as the time from the date of randomization to the earliest of the progression event subsequent to the first subsequent anticancer therapy (excluding radiotherapy) or death. The date of second progression is recorded by the Investigator in the eCRF at each assessment and defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death.	Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months
Durvalumab Versus Durvalumab Plus Tremelimumab: Progression-Free Survival Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	PFS per RECIST 1.1 assessed by BICR is defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdraws from therapy or receives another anticancer therapy prior to progression. PD is defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) - this includes the baseline sum if that is the smallest on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm from nadir.	Response evaluations performed q8w ± 1 week up to 72 weeks, then q12w ± 1 week up to 96 weeks, and then q24w thereafter until PD, up to approximately 89 months
Durvalumab Versus Durvalumab Plus Tremelimumab: Objective Response Rate Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	ORR per RECIST 1.1 assessed by BICR is defined as the percentage of participants with at least 1 visit response of CR or PR (i.e., unconfirmed response). CR is defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm. PR is defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.	From date of randomization until death due to any cause, up to approximately 89 months
Durvalumab Versus Durvalumab Plus Tremelimumab: Overall Survival	OS is defined as the time from the date of randomization until death due to any cause.	From date of randomization until death due to any cause, up to approximately 89 months
Durvalumab Plus Tremelimumab Versus Placebo: Change From Baseline in Patient-Reported Symptoms as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ)	Patient-reported outcomes for 5 disease related symptoms will be assessed using EORTC QLQ-Core 30 (C30) items questionnaire (fatigue, appetite loss) and EORTC QLQ-Lung Cancer module 13 (LC13) (dyspnea, cough and pain in chest). An outcome variable consisting of a score from 0 to 100 will be derived for each of the symptom scales/symptom items, functional scales, and global health status (GHS) scale with higher scores on GHS/QoL and functioning scales representing better health status/function, but higher scores on symptom scales/items representing greater symptom severity.	Baseline (Day 1) and up to approximately 89 months
Durvalumab: Serum Concentration of Durvalumab	Blood samples were collected to determine the concentration of durvalumab.	End of infusion on Cycle 1 Day 1, pre-infusion on Cycle 2 (Week 4), Cycle 5 (Week 16) and Cycle 26 (Week 100) and Month 3 post last dose of study treatment (Week 119) (each treatment cycle is 28 days)
Durvalumab Plus Tremelimumab: Serum Concentration of Tremelimumab	Blood samples will be collected to determine the concentration of tremelimumab.	Up to approximately 27 months
Durvalumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab	Blood samples were collected to determine the presence of ADAs for durvalumab using validated assays. Treatment-emergent ADA-positive was defined as either treatment-induced (post-baseline ADA-positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to ≥4 fold during the study period). Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher level (greater than the analytical variance of the assay) following drug administration. Number of participants with treatment-emergent ADA (ADA incidence) are presented.	From first dose of study drug (Day 1) up to DCO date 15 January 2024 (a maximum of approximately 1936 days)
Durvalumab Plus Tremelimumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab	Blood samples will be collected to determine the presence of ADAs for tremelimumab using validated assays. Treatment-emergent ADA-positive is defined as either treatment-induced (post-baseline ADA-positive only) or treatment-boosted ADA (baseline positive ADA titer that was boosted to ≥4 fold during the study period). Treatment-boosted ADA is defined as a baseline positive ADA titer that was boosted to a 4-fold or higher level (greater than the analytical variance of the assay) following drug administration. Treatment-induced ADA is defined as ADA positive post-baseline and not detected at baseline.	Up to approximately 30 months
Durvalumab Versus Durvalumab Plus Tremelimumab: Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Status Based on Progression-Free Survival, Overall Survival, and Objective Response Rate	Blood samples will be collected for clinical biomarker testing and a tumor specimen will be collected as per tumor specimen collection requirements. The specimen will be evaluated by immunohistochemistry to determine the expression of tumor specific antigens and immune markers. The PD-L1 is a biomarker and will be assessed using the VENTANA PD-L1 (SP263) assay.	Up to approximately 89 months

Other Outcome Measures

Outcome Measure	Time Frame
Adverse Events	Approximately 6 years

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Haiyi Jiang, M.D., AstraZeneca

Publications and helpful links

General Publications

• Senan S, Okamoto I, Lee GW, Chen Y, Niho S, Mak G, Yao W, Shire N, Jiang H, Cho BC. Design and Rationale for a Phase III, Randomized, Placebo-controlled Trial of Durvalumab With or Without Tremelimumab After Concurrent Chemoradiotherapy for Patients With Limited-stage Small-cell Lung Cancer: The ADRIATIC Study. Clin Lung Cancer. 2020 Mar;21(2):e84-e88. doi: 10.1016/j.cllc.2019.12.006. Epub 2019 Dec 28.
• Cheng Y, Spigel DR, Cho BC, Laktionov KK, Fang J, Chen Y, Zenke Y, Lee KH, Wang Q, Navarro A, Bernabe R, Buchmeier EL, Chang JW, Shiraishi Y, Sezgin Goksu S, Badzio A, Shi A, Daniel DB, Hoa NTT, Zemanova M, Mann H, Gowda H, Jiang H, Senan S; ADRIATIC Investigators. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med. 2024 Oct 10;391(14):1313-1327. doi: 10.1056/NEJMoa2404873. Epub 2024 Sep 13.
• Zenke Y, Shiraishi Y, Goto Y, Azuma K, Okishio K, Ogino H, Horio Y, Oizumi S, Hayama M, Nii M, Harada M, Mann H, Olivo YS, Jiang H, Senan S. Durvalumab Post Concurrent Chemoradiotherapy in Japanese Patients With Limited-Stage Small-Cell Lung Cancer in the Phase 3 ADRIATIC Trial. Cancer Sci. 2025 Nov;116(11):3171-3184. doi: 10.1111/cas.70188. Epub 2025 Sep 21.

Helpful Links

• d933qc00001-csp-v5_for redaction_Redacted
• d933qc00001-csp-v1-addendum-eu_Redacted
• Redacted SAP
• Redacted CSR synopsis

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2018
• Primary Completion (Actual): January 15, 2024
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: September 19, 2018
• First Submitted That Met QC Criteria: October 10, 2018
• First Posted (Actual): October 11, 2018

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; Carcinoma; Small Cell Lung Cancer; SCLC; LS-SCLC; Limited Stage
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma; Lung Neoplasms; Small Cell Lung Carcinoma; Substandard Drugs; Pharmaceutical Preparations; durvalumab; tremelimumab
• Other Study ID Numbers: D933QC00001; 2018-000867-10 (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 refer 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