Trial Outcomes & Findings for Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy (NCT NCT03703297)

Last Updated: 2025-11-21

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

730 participants

Primary outcome timeframe

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)

Results posted on

2025-11-21

Participant Flow

This Phase III, double-blind, placebo-controlled trial studied participants with limited stage small-cell lung cancer who had not progressed after concurrent chemoradiation therapy at 164 sites in 19 countries. Interim results are based on data cut-off (DCO) date of 15 January 2024. 730 participants were randomized; the first 600 in a 1:1:1 ratio to durvalumab monotherapy (D), durvalumab plus tremelimumab combination therapy (D+T) or placebo (P), the remaining in a 1:1 ratio to D or P.

Based on the results of the secondary objectives at the interim analysis (reviewed by an unblinded independent data monitoring committee \[IDMC\]), 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.

Participant milestones

Participant milestones
Measure	Durvalumab Participants received durvalumab monotherapy (1500 milligram \[mg\] for participants \>30 kilogram \[kg\] in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via intravenous (IV) infusion once every 4 weeks (q4w), until clinical/Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Durvalumab Plus Tremelimumab Participants received durvalumab in combination with tremelimumab (1500 mg durvalumab in combination with 75 mg tremelimumab for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg durvalumab in combination with 1 mg/kg tremelimumab for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Overall Study STARTED	264	200	266
Overall Study Safety Population	262	0	265
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	264	200	266

Reasons for withdrawal

Reasons for withdrawal
Measure	Durvalumab Participants received durvalumab monotherapy (1500 milligram \[mg\] for participants \>30 kilogram \[kg\] in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via intravenous (IV) infusion once every 4 weeks (q4w), until clinical/Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Durvalumab Plus Tremelimumab Participants received durvalumab in combination with tremelimumab (1500 mg durvalumab in combination with 75 mg tremelimumab for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg durvalumab in combination with 1 mg/kg tremelimumab for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Overall Study Death	115	0	144
Overall Study Withdrawal by Subject	9	0	11
Overall Study Ongoing at the time of DCO	140	200	111

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Durvalumab Plus Tremelimumab n=200 Participants Participants received durvalumab in combination with tremelimumab (1500 mg durvalumab in combination with 75 mg tremelimumab for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg durvalumab in combination with 1 mg/kg tremelimumab for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Total n=730 Participants Total of all reporting groups
Age, Customized <65 years	160 Participants n=68 Participants	NA Participants n=76 Participants	162 Participants n=48 Participants	NA Participants n=33 Participants
Age, Customized >=65 years	104 Participants n=68 Participants	NA Participants n=76 Participants	104 Participants n=48 Participants	NA Participants n=33 Participants
Sex: Female, Male Female	86 Participants n=68 Participants	NA Participants n=76 Participants	78 Participants n=48 Participants	NA Participants n=33 Participants
Sex: Female, Male Male	178 Participants n=68 Participants	NA Participants n=76 Participants	188 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized White	130 Participants n=68 Participants	NA Participants n=76 Participants	137 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=68 Participants	NA Participants n=76 Participants	3 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Asian	131 Participants n=68 Participants	NA Participants n=76 Participants	121 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Other	2 Participants n=68 Participants	NA Participants n=76 Participants	5 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Hispanic or Latino	8 Participants n=68 Participants	NA Participants n=76 Participants	14 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	255 Participants n=68 Participants	NA Participants n=76 Participants	249 Participants n=48 Participants	NA Participants n=33 Participants
Race/Ethnicity, Customized Missing	1 Participants n=68 Participants	NA Participants n=76 Participants	3 Participants n=48 Participants	NA Participants n=33 Participants

PRIMARY outcome

Timeframe: 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)

Population: The FAS included all randomized participants.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab Versus Placebo: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) Per Response Evaluation Criteria in Solid Tumors Version 1.1	16.6 months Interval 10.2 to 28.2	9.2 months Interval 7.4 to 12.9

PRIMARY outcome

Timeframe: From date of randomization until death due to any cause, up to DCO date 15 January 2024 (a maximum of approximately 1936 days)

Population: The FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab Versus Placebo: Overall Survival (OS)	55.9 months Interval 37.3 to NA indicates that upper limit of CI was not estimable due to insufficient number of participants with events at the DCO.	33.4 months Interval 25.5 to 39.9

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause, up to approximately 89 months

OS is defined as the time from the date of randomization until death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: The FAS included all randomized participants. Only participants with measurable disease at baseline per BICR are reported.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=175 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=169 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab Versus Placebo: Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Per Response Evaluation Criteria in Solid Tumors Version 1.1	30.3 percentage of participants	32.0 percentage of participants

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause, up to approximately 89 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 18

Population: The FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
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	48.8 percentage of participants Interval 42.2 to 55.0	36.1 percentage of participants Interval 29.9 to 42.2

SECONDARY outcome

Timeframe: Month 18

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 24

Population: The FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
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	46.2 percentage of participants Interval 39.6 to 52.5	34.2 percentage of participants Interval 28.2 to 40.3

SECONDARY outcome

Timeframe: Month 24

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 24

Population: The FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab Versus Placebo: Percentage of Participants Alive at 24 Months From Randomization (OS24)	68.0 percentage of participants Interval 61.9 to 73.3	58.5 percentage of participants Interval 52.3 to 64.3

SECONDARY outcome

Timeframe: Month 24

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 36

Population: The FAS included all randomized participants.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=264 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo n=266 Participants Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab Versus Placebo: Percentage of Participants Alive at 36 Months From Randomization (OS36)	56.5 percentage of participants Interval 50.0 to 62.5	47.6 percentage of participants Interval 41.3 to 53.7

SECONDARY outcome

Timeframe: Month 36

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause, up to approximately 89 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From date of randomization until death due to any cause, up to approximately 89 months

OS is defined as the time from the date of randomization until death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (Day 1) and up to approximately 89 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

Population: The pharmacokinetic (PK) population included all participants who received at least 1 dose of study drug per the protocol for whom any post-dose data were available and who did not violate or deviate from the protocol in ways that would have significantly affected the PK analyses. Only those participants with data collected at specified timepoints are reported.

Blood samples were collected to determine the concentration of durvalumab.

Outcome measures

Outcome measures
Measure	Durvalumab n=222 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab: Serum Concentration of Durvalumab Cycle 1 Day 1: End of infusion	431.00 microgram per milliliter (mcg/mL) Standard Deviation 327.861	—
Durvalumab: Serum Concentration of Durvalumab Cycle 2 (Week 4): Pre-infusion	89.57 microgram per milliliter (mcg/mL) Standard Deviation 107.228	—
Durvalumab: Serum Concentration of Durvalumab Cycle 5 (Week 16): Pre-infusion	159.63 microgram per milliliter (mcg/mL) Standard Deviation 58.561	—
Durvalumab: Serum Concentration of Durvalumab Cycle 26 (Week 100): Pre-infusion	178.20 microgram per milliliter (mcg/mL) Standard Deviation 65.422	—
Durvalumab: Serum Concentration of Durvalumab Month 3 follow-up	44.97 microgram per milliliter (mcg/mL) Standard Deviation 36.026	—

SECONDARY outcome

Timeframe: Up to approximately 27 months

Blood samples will be collected to determine the concentration of tremelimumab.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose of study drug (Day 1) up to DCO date 15 January 2024 (a maximum of approximately 1936 days)

Population: The ADA population included all participants in the safety analysis set who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result of the study drug.

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.

Outcome measures

Outcome measures
Measure	Durvalumab n=206 Participants Participants received durvalumab monotherapy (1500 mg for participants \>30 kg in weight and a weight-based dosing equivalent to 20 mg/kg for participants \<=30 kg in weight) via IV infusion once q4w, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.	Placebo Participants received matching placebo via IV infusion once q4w for 4 doses/cycles each, until clinical/RECIST 1.1-defined radiological progression, intolerable toxicity, or for a maximum of 24 months, whichever occurred first.
Durvalumab: Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab	7 Participants	—

SECONDARY outcome

Timeframe: Up to approximately 30 months

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 89 months

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.

Outcome measures

Outcome data not reported

Adverse Events

Durvalumab

Serious events: 78 serious events

Other events: 209 other events

Deaths: 115 deaths

Durvalumab Plus Tremelimumab

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 64 serious events

Other events: 196 other events

Deaths: 146 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place