A Study of Durvalumab as Consolidation Therapy in Non-Small Cell Lung Cancer Patients

The PFS per Response Evaluation Criteria in Solid Tumors 1.1. (RECIST 1.1) using blinded independent central review (BICR) assessments 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 anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of \>=5 millimeters (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: The mITT set included all randomized participants who were without sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Patient reported outcomes for 5 disease related symptoms was assessed using EORTC QLQ-Core 30 (C30) items questionnaire (fatigue, appetite loss) and EORTC QLQ-Lung Cancer module 13 (LC13) (dyspnoea, cough and pain in chest).An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, functional scales, and global health status scale with higher scores on global health status/QoL and functioning scales representing better health status/function, but higher scores on symptom scales/items representing greater symptom severity. An improvement in symptoms were indicated by a negative change in score from baseline. A positive change in score from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as change from baseline of \>=10. Change from baseline in C30: global health status/QoL, physical functioning, fatigue, appetite loss and LC13: dyspnoea, cough and pain in chest are presented.

Time frame: Baseline (Day 1) and Week 132

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only those participants with data collected at specified timepoints are reported.

The DoR per RECIST 1.1 using BICR was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of \>=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. The DoR was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only responders (participants with objective response) are analyzed and reported.

Blood samples were collected to determine the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence was defined as the number of participants with positive ADA result at any time, baseline or post-baseline. ADA incidence 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 only post-baseline and not detected at baseline. Persistently positive was defined as having at least 2 post-baseline ADA positive assessments with at least 16 weeks between the first and last positive assessment, or ADA positive at the last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment without fulfilling the conditions for persistently positive.

Time frame: Pre-dose on Day 1 of Cycles 1, 2 and 4 (each cycle=28 days)

Population: ADA analysis set included all participants who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA result.

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 data for number of participants with its positive status will be presented.

Time frame: Up to 9 years

The ORR per RECIST 1.1 using BICR was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) based on all participants in the subset of the analysis population including only those participants with measurable disease at baseline per BICR. The CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10 mm. The PR was defined as at least a 30% decrease in the sum of the diameters of TLs, taking as reference the baseline sum of diameters as long as criteria for PD are not met.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants. Only those participants with measurable disease at baseline per BICR are reported.

The OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy. Median OS was calculated using the Kaplan-Meier technique.

Time frame: Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

The PFS per RECIST 1.1 using BICR assessments 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 anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of \>=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. The PFS12 and PFS18 were defined as the Kaplan-Meier estimate of PFS per RECIST 1.1 as assessed by the Investigator at 12 and 18 months, respectively and both were obtained using the algorithm for the RECIST 1.1 site Investigator tumor data.

Time frame: Months 12 and 18

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy. The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months after randomization.

Time frame: Month 24

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

The PFS per RECIST 1.1 using BICR assessments 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 anti-cancer therapy prior to progression. The PD was defined as at least a 20% increase in the sum of diameters of target lesions and an absolute increase of \>=5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: The ITT set included all randomized participants.

Blood samples were collected to determine the concentration of durvalumab.

Time frame: End of infusion on Cycle 1 Day 1, pre-infusion on Cycles 2 and 4 Day 1 and Month 3 follow-up (each cycle=28 days)

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

PFS2 was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy, or death. The date of the second progression was recorded by the Investigator and defined according to local standard clinical practice and could have involved any of objective radiological imaging, symptomatic progression, or death. Median time to PFS2 was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.

TTDM as per RECIST 1.1 using BICR was 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 was defined as any new lesion that was outside of the radiation field according to RECIST 1.1. Median TTDM was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at screening, every 8 weeks ±1 week up to 48 weeks, and then every 12 weeks ±1 week thereafter until confirmed PD. Assessed up to the DCO date 23-Jun-2024 (a maximum of approximately 2035 days)

Population: Analysis was performed on the mITT and ITT set. The mITT set included all randomized participants who were without sensitizing EGFR mutations or ALK rearrangements. The ITT set included all randomized participants.