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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

Blood samples were collected to determine the concentration of durvalumab.

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

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.

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.

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.