NCT03043872

Brief Summary

This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of combining durvalumab ± tremelimumab with platinum based chemotherapy (EP) followed by durvalumab ± tremelimumab maintenance therapy versus EP alone as first-line treatment in patients with extensive-stage small-cell lung cancer

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
987

participants targeted

Target at P75+ for phase_3

Timeline
8mo left

Started Mar 2017

Longer than P75 for phase_3

Geographic Reach
23 countries

207 active sites

Status
active not recruiting

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

Study Progress93%
Mar 2017Dec 2026

First Submitted

Initial submission to the registry

January 18, 2017

Completed
19 days until next milestone

First Posted

Study publicly available on registry

February 6, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

March 27, 2017

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 27, 2020

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

March 4, 2021

Completed
5.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Expected
Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

2.8 years

First QC Date

January 18, 2017

Results QC Date

January 21, 2021

Last Update Submit

April 9, 2026

Conditions

Keywords

Carcinoma, Small Cell LungOat Cell Carcinoma of LungOat Cell Lung CancerSmall Cell Cancer Of The LungSmall Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

  • Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP

    OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An interim analysis of OS in the global cohort was pre-specified after approximately 318 OS events occurred each between the D + EP and EP groups (60% maturity), and between the D + T + EP and EP groups (60% maturity). At the global cohort interim analysis DCO (11 March 2019), comparison of OS in the D + EP versus (vs) EP groups had crossed the pre-specified boundary. Since these results were considered final in terms of formal statistical testing, they are presented here as a primary outcome measure. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the global cohort final analysis is presented separately in the subsequent primary outcome measure.

    From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).

  • OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP

    OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This primary outcome measure presents OS for the analysis of D + EP vs EP and D + T + EP vs EP at the time of the global cohort final analysis DCO (27 January 2020). Analysis of D + EP vs EP at the global cohort interim analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (global cohort final analysis) is presented as a secondary outcome measure.

    From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

  • OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP

    OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure.

    From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).

  • OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP

    OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure.

    From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Secondary Outcomes (28)

  • OS in the Global Cohort; D + T + EP Compared With D + EP

    From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

  • Progression-Free Survival (PFS) in the Global Cohort

    Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

  • Objective Response Rate (ORR) in the Global Cohort

    Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

  • Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort

    Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

  • Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort

    Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

  • +23 more secondary outcomes

Study Arms (3)

Arm 1

EXPERIMENTAL

durvalumab+tremelimumab+EP (carboplatin or cisplatin + etoposide)

Drug: DurvalumabDrug: TremelimumabDrug: CarboplatinDrug: CisplatinDrug: Etoposide

Arm 2

EXPERIMENTAL

durvalumab+EP (carboplatin or cisplatin + etoposide)

Drug: DurvalumabDrug: CarboplatinDrug: CisplatinDrug: Etoposide

Arm 3

ACTIVE COMPARATOR

EP (carboplatin or cisplatin + etoposide)

Drug: CarboplatinDrug: CisplatinDrug: Etoposide

Interventions

IV infusions every 3 weeks for 12 weeks (4 cycles) and every 4 weeks thereafter until PD or other discontinuation criteria.

Arm 1Arm 2

IV infusions every 3 weeks for 12 weeks(4 cycles). An additional dose of tremelimumab will be administered in the week 16.

Arm 1

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Arm 1Arm 2Arm 3

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Arm 1Arm 2Arm 3

up to 4 cycles every 3 weeks in Arm 1 and 2, up to 6 cycles every 3 weeks in Arm 3

Arm 1Arm 2Arm 3

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically documented extensive disease. Brain metastases; must be asymptomatic or treated and stable off steroids and anti-convulsants for at least 1 month prior to study treatment.
  • Suitable to receive a platinum-based chemotherapy regimen as 1st line treatment.
  • Life expectancy ≥12 weeks at Day 1.
  • ECOG 0 or 1 at enrolment.
  • No prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines.

You may not qualify if:

  • Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest).
  • Paraneoplastic syndrome of autoimmune nature, requiring systemic treatment or clinical symptomatology suggesting worsening of PNS
  • Active infection including tuberculosis, HIV, hepatitis B anc C
  • Active or prior documented autoimmune or inflammatory disorders
  • Uncontrolled intercurrent illness, including but not limited to interstitial lung disease.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (207)

Research Site

Birmingham, Alabama, 35235, United States

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Scottsdale, Arizona, 85259, United States

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Rogers, Arkansas, 72758, United States

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Santa Monica, California, 90404, United States

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New Haven, Connecticut, 06520, United States

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Athens, Georgia, 30607, 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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Leawood, Kansas, 66209, United States

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Wichita, Kansas, 67214, United States

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Paducah, Kentucky, 42003, United States

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Grand Rapids, Michigan, 49503, United States

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Mineola, New York, 11501, United States

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Cleveland, Ohio, 44106, United States

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Columbus, Ohio, 43219, United States

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Harrisburg, Pennsylvania, 17109, United States

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Sioux Falls, South Dakota, 57104, United States

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Nashville, Tennessee, 37203, United States

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Kennewick, Washington, 99336, United States

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Buenos Aires, C1118AAT, Argentina

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Ciudad de Buenos Aires, C1426, Argentina

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Mar del Plata, 7600, Argentina

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Rosario, 2000, Argentina

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San Miguel de Tucumán, T4000IAK, Argentina

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Linz, 4021, Austria

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Salzburg, 5020, Austria

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Vienna, 1140, Austria

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Vienna, 1210, Austria

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Barretos, 14784-400, Brazil

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Curitiba, 81520-060, Brazil

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Passo Fundo, 99010 260, Brazil

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Porto Alegre, 91350-200, Brazil

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Ribeirão Preto, 14048-900, Brazil

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Rio de Janeiro, 22793-080, Brazil

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Salvador, 41.950-610, Brazil

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Santo André, 09060-650, Brazil

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São José do Rio Preto, 15090-000, Brazil

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São Paulo, 03102-002, Brazil

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Panagyurishte, 4500, Bulgaria

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Plovdiv, 4000, Bulgaria

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Plovdiv, 4004, Bulgaria

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Sofia, 1330, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1618, Bulgaria

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Sofia, 1784, Bulgaria

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Varna, 9010, Bulgaria

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Beijing, 100142, China

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Beijing, 100730, China

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Beijing, 100853, China

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Bengbu, 233004, China

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Changchun, 130021, China

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Changsha, 410013, China

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Chengdu, 610041, China

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Chongqing, 400038, China

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Hangzhou, 310003, China

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Hangzhou, 310006, China

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Hangzhou, 310009, China

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Hefei, 230601, China

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Nanchang, 330006, China

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Nanjing, 210009, China

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Nanjing, 210029, China

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Shanghai, 200032, China

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Shanghai, 200433, China

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Shenyang, 110042, China

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Ürümqi, 830000, China

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Wenzhou, 325000, China

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Wuhan, 430022, China

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Wuhan, 430030, China

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Xi'an, 710038, China

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Xi'an, 710061, China

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Zhanjiang, 524001, China

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Zhengzhou, 450008, China

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Zhuhai, 519099, China

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Brno, 639 00, Czechia

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Olomouc, 775 21, Czechia

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Ostrava - Vitkovice, 703 84, Czechia

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Prague, 128 08, Czechia

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Prague, 140 59, Czechia

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Prague, CZ-150 18, Czechia

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Avignon, 84918, France

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Brest, 29609, France

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Créteil, 94010, France

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La Tronche, 38043, France

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Pierre-Bénite, 69310, France

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Rennes, 35033, France

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Aachen, 52074, Germany

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Berlin, 13125, Germany

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Gauting, 82131, Germany

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Gera, 07548, Germany

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Hamburg, 20251, Germany

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Heidelberg, 69126, Germany

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Mainz, 55131, Germany

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Regensburg, 93053, Germany

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Budapest, 1083, Hungary

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Budapest, 1106, Hungary

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Budapest, 1121, Hungary

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Budapest, 1134, Hungary

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Deszk, 6772, Hungary

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Gyula, 5700, Hungary

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Kaposvár, 7400, Hungary

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Kecskemét, 6000, Hungary

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Miskolc, 3529, Hungary

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Pécs, 7624, Hungary

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Székesfehérvár, 8000, Hungary

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Jerusalem, 91031, Israel

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Kfar Saba, 95847, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5265601, Israel

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Bergamo, 24127, Italy

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Meldola, 47014, Italy

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Milan, 20133, Italy

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Palermo, 90146, Italy

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Roma, 00100, Italy

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Terni, 05100, Italy

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Chūōku, 104-0045, Japan

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Fukuoka, 812-8582, Japan

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Fukushima, 960-1295, Japan

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Himeji-shi, 670-8520, Japan

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Iwakuni-shi, 740-8510, Japan

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Kashiwa, 227-8577, Japan

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Kōtoku, 135-8550, Japan

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Kurume-shi, 830-0011, Japan

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Kyoto, 606-8507, Japan

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Matsuyama, 791-0280, Japan

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Nagoya, 464-8681, Japan

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Nagoya, 466-8560, Japan

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Okayama, 700-8558, Japan

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Sakaishi, 591-8555, Japan

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Sayama, 589-8511, Japan

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Tokushima, 770-8503, Japan

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Ube-shi, 755-0241, Japan

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Yokohama, 236-0004, Japan

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Yokohama, 241-8515, Japan

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Amsterdam, 1066 CX, Netherlands

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Arnhem, 6815 AD, Netherlands

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Groningen, 9713 GZ, Netherlands

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Hengelo, 7555 DL, Netherlands

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Maastricht, 6202 AZ, Netherlands

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Rotterdam, 3015 GD, Netherlands

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Bialystok, 15-027, Poland

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Bialystok, 15-540, Poland

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Lublin, 20-954, Poland

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Olsztyn, 10-357, Poland

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Warsaw, 02-781, Poland

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Cluj-Napoca, 400015, Romania

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Floreşti, 407280, Romania

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Suceava, 720237, Romania

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Moscow, 105229, Russia

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Omsk, 644013, Russia

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Rostov-on-Don, 344037, Russia

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Saint Petersburg, 194291, Russia

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Saint Petersburg, 195271, Russia

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Saint Petersburg, 196603, Russia

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Saint Petersburg, 197758, Russia

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Ufa, 450054, Russia

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Banská Bystrica, 97517, Slovakia

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Bardejov, 085 01, Slovakia

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Bratislava, 82606, Slovakia

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Bratislava, 833 01, Slovakia

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Košice, 041 91, Slovakia

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Nové Zámky, 940 01, Slovakia

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Trnava, 91708, Slovakia

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Changwon, 51353, South Korea

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Cheongju-si, 28644, South Korea

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Daegu, 42415, South Korea

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Incheon, 21565, South Korea

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Jinju, 660-702, South Korea

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Seongnam-si, 13620, South Korea

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Seongnam-si, 463-712, South Korea

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Seoul, 05505, South Korea

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Seoul, 110746, South Korea

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A Coruña, 15006, Spain

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Badajoz, 06008, Spain

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Badalona, 08916, Spain

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Barcelona, 08041, Spain

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Madrid, 08035, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Santander, 39008, Spain

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Valencia, 46010, Spain

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Zaragoza, 50009, Spain

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Changhua, 50006, Taiwan

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Kaohsiung City, 82445, Taiwan

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Kaohsiung City, 83301, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 704, Taiwan

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Tainan, 736, Taiwan

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Taipei, 11217, Taiwan

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Taipei, 235, Taiwan

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Ankara, 06230, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Edirne, 22030, Turkey (Türkiye)

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Istanbul, 32098, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Izmir, 35620, Turkey (Türkiye)

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Dnipro, 49102, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kirovohrad, 25006, Ukraine

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Kryvyi Rih, 50048, Ukraine

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Kyiv, 03022, Ukraine

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Kyiv, 03115, Ukraine

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Lviv, 79031, Ukraine

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Odesa, 65055, Ukraine

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Sumy, 40022, Ukraine

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Vinnytsia, 21029, Ukraine

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Zaporizhzhia, 69040, Ukraine

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Related Publications (4)

  • Ozguroglu M, Goldman JW, Chen Y, Garassino MC, Medic N, Mann H, Chugh P, Dalvi T, Paz-Ares L. Adverse events self-reported by patients with extensive-stage small-cell lung cancer in the phase III CASPIAN study. Future Oncol. 2025 May;21(12):1511-1523. doi: 10.1080/14796694.2025.2491297. Epub 2025 May 7.

  • Xie M, Vuko M, Rodriguez-Canales J, Zimmermann J, Schick M, O'Brien C, Paz-Ares L, Goldman JW, Garassino MC, Gay CM, Heymach JV, Jiang H, Barrett JC, Stewart RA, Lai Z, Byers LA, Rudin CM, Shrestha Y. Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study. Mol Cancer. 2024 May 30;23(1):115. doi: 10.1186/s12943-024-02014-x.

  • Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. doi: 10.1016/S1470-2045(20)30539-8. Epub 2020 Dec 4.

  • Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Ozguroglu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. doi: 10.1016/S0140-6736(19)32222-6. Epub 2019 Oct 4.

Related Links

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumabtremelimumabCarboplatinCisplatinEtoposide

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination ComplexesOrganic ChemicalsChlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsPolycyclic CompoundsGlucosidesGlycosidesCarbohydrates

Limitations and Caveats

Analysis of the China cohort was performed to evaluate the consistency of efficacy and safety in Chinese patients with the global cohort in order to meet regulatory requirements and was not powered for a formal assessment of statistical significance.

Results Point of Contact

Title
Global Clinical Lead
Organization
AstraZeneca

Study Officials

  • Haiyi Jiang, M.D.

    AstraZeneca

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 18, 2017

First Posted

February 6, 2017

Study Start

March 27, 2017

Primary Completion

January 27, 2020

Study Completion (Estimated)

December 31, 2026

Last Updated

April 22, 2026

Results First Posted

March 4, 2021

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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