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)
2 other identifiers
interventional
730
19 countries
183
Brief Summary
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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Sep 2018
Longer than P75 for phase_3
183 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
September 19, 2018
CompletedStudy Start
First participant enrolled
September 27, 2018
CompletedFirst Posted
Study publicly available on registry
October 11, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 15, 2024
CompletedResults Posted
Study results publicly available
August 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 23, 2026
ExpectedNovember 21, 2025
November 1, 2025
5.3 years
September 19, 2018
May 23, 2025
November 14, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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 Outcomes (23)
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
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
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
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
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
Month 18
- +18 more secondary outcomes
Study Arms (3)
Durvalumab + Placebo
EXPERIMENTALDurvalumab 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.
Durvalumab + Tremelimumab
EXPERIMENTALDurvalumab 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.
Placebo + Placebo
PLACEBO COMPARATORPlacebo: 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.
Interventions
Durvalumab IV (intravenous infusion)
Eligibility Criteria
You may qualify if:
- Histologically or cytologically documented limited-stage small cell lung cancer (stage I-III).
- 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.
- 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.
- Have not progressed following definitive concurrent chemoradiation 5 .Life expectancy ≥ 12 weeks at Day 1. 6. ECOG 0 or 1 at enrolment.
You may not qualify if:
- Extensive-stage SCLC
- Active or prior documented autoimmune or inflammatory disorders
- Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.
- Active infection including tuberculosis, HIV, hepatitis B and C
- Patients who received sequential chemotherapy and radiotherapy (no overlap of RT with chemotherapy)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (183)
Research Site
Tucson, Arizona, 85715, United States
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Santa Rosa, California, 95403, United States
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New Haven, Connecticut, 06510, United States
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Fort Myers, Florida, 33901, United States
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Orange City, Florida, 32763, United States
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St. Petersburg, Florida, 33705, United States
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Marietta, Georgia, 30060, United States
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Hines, Illinois, 60141, United States
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Fort Wayne, Indiana, 46804, United States
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Muncie, Indiana, 47303, United States
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Lexington, Kentucky, 40536, United States
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Annapolis, Maryland, 21401, United States
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Baltimore, Maryland, 21287, United States
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Towson, Maryland, 21204, United States
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Boston, Massachusetts, 02114, United States
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Detroit, Michigan, 48201, United States
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Grand Rapids, Michigan, 49503, United States
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Minneapolis, Minnesota, 55407, United States
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Summit, New Jersey, 07902, United States
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New Hyde Park, New York, 11042, United States
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Chapel Hill, North Carolina, 27599, United States
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Portland, Oregon, 97239, United States
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Philadelphia, Pennsylvania, 19111, United States
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Pittsburgh, Pennsylvania, 15212, United States
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Sioux Falls, South Dakota, 57104, United States
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Chattanooga, Tennessee, 37404, United States
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Nashville, Tennessee, 37203, United States
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Nashville, Tennessee, 37232, United States
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Dallas, Texas, 75390, United States
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Kennewick, Washington, 99336, United States
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Tacoma, Washington, 98405, United States
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Charleston, West Virginia, 25304, United States
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Huntington, West Virginia, 25701, United States
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Milwaukee, Wisconsin, 53226, United States
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CABA, C1012AAR, Argentina
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Ciudad de Buenos Aires, C1280AEB, Argentina
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Córdoba, X5004BAL, Argentina
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Mar del Plata, 7600, Argentina
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Rosario, 2000, Argentina
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Aalst, 9300, Belgium
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Anderlecht, 1070, Belgium
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Brussels, 1200, Belgium
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Hasselt, 3500, Belgium
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Roeselare, 8800, Belgium
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Edmonton, Alberta, T6G 1Z2, Canada
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Toronto, CA, M5G 2M9, Canada
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Winnipeg, Manitoba, R3E 0V9, Canada
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Hamilton, Ontario, L8V 5C2, Canada
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London, Ontario, N6A 5W9, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, Canada
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Montreal, Quebec, H4A 3J1, Canada
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Beijing, 100021, China
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Beijing, 100036, China
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Beijing, 100142, China
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Beijing, 100191, China
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Beijing, 100730, China
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Bengbu, 233004, China
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Changchun, 130000, China
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Changsha, 410013, China
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Chengdu, 610042, China
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Chongqing, 400030, China
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Chongqing, 400042, China
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Fuzhou, 350011, China
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Hangzhou, 310003, China
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Hefei, 230601, China
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Shanghai, 200030, China
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Shanghai, 200032, China
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Shenyang, 110001, China
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Shenyang, 110042, China
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Tianjin, 300060, China
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Wuhan, 430010, China
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Wuhan, 430022, China
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Wuhan, 430030, China
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Yangzhou, 225001, China
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Zhengzhou, 450008, China
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Brno, 639 00, Czechia
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Olomouc, 77900, Czechia
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Ostrava, 703 00, Czechia
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Prague, 128 08, Czechia
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Prague, 140 59, Czechia
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Berlin, 12351, Germany
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Cologne, 51109, Germany
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Freiburg im Breisgau, 79106, Germany
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Gauting, 82131, Germany
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Heidelberg, 69126, 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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Regensburg, 93053, Germany
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Stuttgart, 70376, Germany
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Würzburg, 97080, Germany
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Bengaluru, 560076, India
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Gūrgaon, 122001, India
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Brescia, 25123, Italy
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Milan, 20133, Italy
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Milan, 20141, Italy
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Orbassano, 10043, Italy
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Parma, 43126, Italy
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Roma, 00100, Italy
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Rozzano, 20089, Italy
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Terni, 05100, Italy
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Bunkyō City, 160-0023, Japan
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Chūōku, 104-0045, Japan
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Fukuoka, 812-8582, Japan
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Iwakuni-shi, 740-8510, Japan
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Kashiwa, 277-8577, Japan
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Kōtoku, 135-8550, Japan
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Kurume-shi, 830-0011, Japan
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Nagoya, 464-8681, Japan
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Nagoya, 466-8560, Japan
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Niigata, 951-8566, Japan
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Sakaishi, 591-8555, Japan
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Sapporo, 003-0804, Japan
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Sayama, 589-8511, Japan
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Sendai, 980-0873, Japan
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Sunto-gun, 411-8777, Japan
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Tokushima, 770-8503, Japan
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Ube-shi, 755-0241, Japan
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's-Hertogenbosch, 5223 GZ, Netherlands
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Amsterdam, 1081 HV, Netherlands
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Groningen, 9713 GZ, Netherlands
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Harderwijk, 3844 DG, Netherlands
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Hengelo, 7555 DL, Netherlands
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Gdansk, 80-952, Poland
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Olsztyn, 10-357, Poland
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Poznan, 60-569, Poland
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Tomaszów Mazowiecki, 97-200, Poland
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Warsaw, 02-781, Poland
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Wroclaw, 53-413, Poland
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Kazan', 420029, Russia
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Kirov, 610021, Russia
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Moscow, 105229, Russia
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Moscow, 115478, Russia
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Moscow, 125284, Russia
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Obninsk, 249036, Russia
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Omsk, 644013, Russia
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Ufa, 450054, Russia
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Volgograd, 400138, Russia
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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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Goyang-si, 10408, South Korea
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Jinju, 52727, South Korea
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Seongnam-si, 13620, South Korea
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Seoul, 03080, South Korea
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Seoul, 03722, South Korea
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Seoul, 05505, South Korea
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Suwon, 16499, South Korea
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Barcelona, 08003, Spain
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Barcelona, 08035, Spain
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Madrid, 28034, Spain
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Madrid, 28040, Spain
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Madrid, 28041, Spain
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Oviedo, 33011, Spain
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Seville, 41013, Spain
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Valencia, 46026, Spain
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Zaragoza, 50009, Spain
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Hsinchu, 300, Taiwan
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Kaohsiung City, 83301, Taiwan
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Keelung, 20445, Taiwan
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Taichung, 40705, Taiwan
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Tainan, 70403, Taiwan
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Tainan, 736, Taiwan
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Taipei, 112, Taiwan
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Taipei, 235, Taiwan
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Taoyuan, 333, Taiwan
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Yunlin, 640, Taiwan
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Adana, 01060, Turkey (Türkiye)
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Ankara, 06230, Turkey (Türkiye)
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Ankara, 06280, Turkey (Türkiye)
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Antalya, 07059, Turkey (Türkiye)
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Edirne, 22030, Turkey (Türkiye)
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Istanbul, 34030, Turkey (Türkiye)
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Izmir, 35620, Turkey (Türkiye)
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Konya, 42080, Turkey (Türkiye)
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Samsun, Turkey (Türkiye)
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Manchester, M20 4BX, United Kingdom
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Truro, TR1 3LJ, United Kingdom
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Hanoi, 100000, Vietnam
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Hà Nội, 100000, Vietnam
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Ho Chi Minh City, 700000, Vietnam
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Ho Chi Minh City, 70000, Vietnam
Related Publications (3)
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.
PMID: 40976711DERIVEDCheng 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.
PMID: 39268857DERIVEDSenan 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.
PMID: 31948903DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Based on the results of the secondary objectives at the interim analysis (reviewed by an unblinded IDMC), data for the D+T arm were to remain blinded to the Sponsor as pre-specified in the study's unblinding plan. Since the D+T arm was blinded at the time of posting the results from this interim analysis, results for that arm will be posted at the time of final analysis.
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Study Officials
- STUDY DIRECTOR
Haiyi Jiang, M.D.
AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 19, 2018
First Posted
October 11, 2018
Study Start
September 27, 2018
Primary Completion
January 15, 2024
Study Completion (Estimated)
October 23, 2026
Last Updated
November 21, 2025
Results First Posted
August 1, 2025
Record last verified: 2025-11
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 refer 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.