NCT03703297 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2025-11-21

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Durvalumab Versus Placebo: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1

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outcome · POSTED

Durvalumab Versus Placebo: Overall Survival (OS)

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outcome · NOT POSTED

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

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab Combination Versus Placebo: Overall Survival

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outcome · POSTED

Durvalumab Versus Placebo: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1

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outcome · NOT POSTED

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

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outcome · POSTED

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

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outcome · NOT POSTED

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

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outcome · POSTED

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

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outcome · NOT POSTED

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

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outcome · NOT POSTED

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

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outcome · POSTED

Durvalumab Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization (OS24)

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization

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outcome · POSTED

Durvalumab Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization (OS36)

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab Combination Versus Placebo: Time From Randomization to Second Progression (PFS2)

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outcome · NOT POSTED

Durvalumab Versus Durvalumab Plus Tremelimumab: Progression-Free Survival Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1

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outcome · NOT POSTED

Durvalumab Versus Durvalumab Plus Tremelimumab: Objective Response Rate Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1

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outcome · NOT POSTED

Durvalumab Versus Durvalumab Plus Tremelimumab: Overall Survival

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outcome · NOT POSTED

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)

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outcome · POSTED

Durvalumab: Serum Concentration of Durvalumab

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab: Serum Concentration of Tremelimumab

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outcome · POSTED

Durvalumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab

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outcome · NOT POSTED

Durvalumab Plus Tremelimumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab

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outcome · NOT POSTED

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

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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)
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Durvalumab
Other: Placebo
label
Durvalumab + Placebo
type
EXPERIMENTAL
description
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.
intervention Names
Drug: Durvalumab
Drug: Tremelimumab
label
Durvalumab + Tremelimumab
type
EXPERIMENTAL
description
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.
intervention Names
Other: Placebo
label
Placebo + Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Durvalumab + Placebo
Durvalumab + Tremelimumab
description
Durvalumab IV (intravenous infusion)
name
Durvalumab
other Names
MEDI4736
type
DRUG
arm Group Labels
Durvalumab + Tremelimumab
description
Tremelimumab IV (intravenous infusion)
name
Tremelimumab
type
DRUG
arm Group Labels
Durvalumab + Placebo
Placebo + Placebo
description
Placebo IV (intravenous infusion)
name
Placebo
type
OTHER

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: TRIPLE
who Masked: PARTICIPANT
CARE_PROVIDER
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 730
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Durvalumab Versus Placebo: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1
time Frame
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)
description
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.
measure
Durvalumab Versus Placebo: Overall Survival (OS)
time Frame
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

description
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.
measure
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
time Frame
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
description
OS is defined as the time from the date of randomization until death due to any cause.
measure
Durvalumab Plus Tremelimumab Combination Versus Placebo: Overall Survival
time Frame
From date of randomization until death due to any cause, up to approximately 89 months
description
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.
measure
Durvalumab Versus Placebo: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1
time Frame
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)
description
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.
measure
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
time Frame
From date of randomization until death due to any cause, up to approximately 89 months
description
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.
measure
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
time Frame
Month 18
description
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.
measure
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
time Frame
Month 18
description
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.
measure
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
time Frame
Month 24
description
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.
measure
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
time Frame
Month 24
description
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.
measure
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
time Frame
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
description
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.
measure
Durvalumab Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization (OS24)
time Frame
Month 24
description
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.
measure
Durvalumab Plus Tremelimumab Combination Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization
time Frame
Month 24
description
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.
measure
Durvalumab Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization (OS36)
time Frame
Month 36

Full study description

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

Source references

references

citation
Senan S, Cho BC, Laktionov KK, Zenke Y, Lee KH, Wang Q, Navarro A, Buchmeier EL, Goksu SS, Badzio A, Shi A, Daniel DB, Zemanova M, Iyengar P, Paz-Ares L, Szadkowski L, Chugh P, Lai WV, Spigel DR. Durvalumab Consolidation in Limited-Stage SCLC: Outcomes by Prior Concurrent Chemoradiotherapy and Prophylactic Cranial Irradiation in the Phase 3 ADRIATIC Trial. J Thorac Oncol. 2026 Aug;21(8):103703. doi: 10.1016/j.jtho.2026.103703. Epub 2026 Mar 30.
pmid
41921748
type
DERIVED
citation
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
40976711
type
DERIVED
citation
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.
pmid
39268857
type
DERIVED
citation
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.
pmid
31948903
type
DERIVED