Study of Durvalumab Given With Chemoradiation Therapy in Patients With Unresectable Non-small Cell Lung Cancer

The PFS per Response Evaluation Criteria in Solid Tumors, version 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 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. Median PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.

Patient reported outcomes for 5 disease related symptoms was assessed using the EORTC QLQ-Core 30 (C30) items questionnaire (fatigue and appetite loss) and the EORTC QLQ-Lung Cancer module 13 (LC13) (dysponea, cough and chest pain). An outcome variable consisting of a total score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status scale with higher scores on the global health status/quality of life (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 a change from baseline of \>=10.

Time frame: At screening, 2, 4, 6, 8, 12, 16, and 20 weeks after randomization, then every 8 weeks ±1 week up to 52 weeks, and then every 12 weeks ±1 week thereafter until PFS2. Assessed up to 12 months.

Population: The FAS included all randomized participants. Only participants analyzed at baseline through Month 12 are reported.

The CRR per RECIST 1.1 using BICR was defined as the percentage of participants with a confirmed response of CR. The CR was defined as disappearance of all target lesions since baseline.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.

The DCR at 24 weeks per RECIST 1.1 using BICR was defined as the percentage of participants who had a best objective response of CR or PR in the first 25 weeks (to allow for late assessment within the assessment window) or who had stable disease for \>= 23 weeks after randomization (to allow for an early assessment within the ± 1 week assessment window).

Time frame: Week 24

Population: The FAS included all randomized participants.

The DoR per RECIST 1.1 using BICR was defined as the time from the date of first documented response (which was subsequently confirmed) until the first date of documented progression or death in the absence of PD. The CR was defined as disappearance of all target lesions since baseline. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions. The DoR was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants. Only participants with objective response are analyzed.

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

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

The ORR per RECIST 1.1 using BICR was defined as the percentage of participants with a confirmed response of complete response (CR) or partial response (PR) based on all participants in the FAS. The CR was defined as disappearance of all target lesions since baseline. The PR was defined as at least a 30% decrease in the sum of the diameters of target lesions.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.

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: From screening until confirmed PD, assessed up to the DCO date (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.

The OS24 was defined as the Kaplan-Meier estimate of OS at 24 months. Median OS24 was calculated using the Kaplan-Meier technique.

Time frame: Month 24

Population: The FAS included all randomized participants.

An AE is the development of any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. A SAE is an AE occurring during any study phase, that fulfils 1 or more of the following criteria: death, life-threatening, in-participant hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital abnormality or birth defect, and an important medical event that may jeopardize the participant or may require medical treatment to prevent 1 of the outcomes listed above. AEs leading to discontinuation of study treatment were those with action taken was 'Drug Permanently Discontinued' for any study treatment.

Time frame: From time of signature of informed consent up to 90 days after last dose of study treatment or up to the date of initiation of the first subsequent therapy, whichever occurs first, approximately 1988 days.

Population: The Safety analysis set included all participants who received at least 1 dose of randomized treatment.

Blood samples were collected to determine the concentration of durvalumab.

Time frame: End of infusion on Week 0, pre-infusion on Weeks 4 and 12, and Month 3 follow-up

Population: The Pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of durvalumab or matching placebo per protocol, for whom any post-dose data were available and did not violate or deviate from the protocol in ways that would significantly affect the PK analyses. Only participants analyzed at specific timepoint are reported.

The PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS per Investigator assessment) 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, symptomatic progression, or death. Median PFS2 was calculated using the Kaplan-Meier technique.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.

The TTDM 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 the radiation field according to RECIST 1.1 or proven by biopsy.

Time frame: Tumour scans performed at screening, 16 weeks ±1 week after randomization, then 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 (a maximum of approximately 1988 days).

Population: The FAS included all randomized participants.