A Global Study to Assess the Effects of MEDI4736 Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

OS was defined as the time from the date of randomization until death due to any cause. OS was calculated using the Kaplan-Meier technique.

Time frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.

PFS was defined as the time from randomization until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression). Progression was defined using RECIST 1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. PFS was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.

Population: FAS included all randomized patients, analyzed on an intent-to-treat (ITT) basis.

DoR was defined as the time from date for first documented response of CR or PR until the first documented response of progression per RECIST 1.1 or death in the absence of progression. DoR was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis. Only patients with an objective response were included in the analysis.

ADA positive post-baseline only was also referred to as treatment-induced ADA positive. Treatment-boosted ADA was defined as baseline positive ADA titer that was boosted by ≥4-fold following drug administration. Persistently positive was defined as positive at ≥2 post-baseline assessments (with ≥16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. Confirmed ADA positive samples were subsequently tested in a neutralizing antibody assay.

Time frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48. Analysis performed at 22 Mar 2018 DCO.

Population: ADA evaluable population included patients who had non-missing baseline ADA and at least 1 non-missing post-baseline ADA results.

ORR was defined as the percentage of patients with at least one visit response of Complete Response (CR) or Partial Response (PR) per RECIST 1.1 for target lesions: CR: Disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS (which included all randomized patients) with measureable disease at baseline, analyzed on an ITT basis.

OS24 was defined as the percentage of patients who were alive at 24 months after randomization per the Kaplan-Meier estimate of OS at 24 months.

Time frame: From baseline until death due to any cause. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.

To evaluate PK, blood samples were collected pre-dose and post-dose and trough and peak serum concentrations of durvalumab, respectively, were determined. Pre-dose samples were taken within 60 minutes before infusion and post-dose samples were taken within 10 minutes after the end of infusion.

Time frame: Samples were collected pre-dose on Day 1 (Week 0), Week 8, Week 24 and Week 48, and post-dose on Day 1 (Week 0) and Week 24. Analysis performed at 22 Mar 2018 DCO.

Population: PK analysis set included all patients who received at least 1 dose of durvalumab 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 significantly affect the PK analyses.

APF12 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 12 months after randomization per Kaplan-Meier estimate of PFS at 12 months.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.

APF18 was defined as the percentage of patients who were alive and progression free per RECIST 1.1 at 18 months after randomization per the Kaplan-Meier estimate of PFS at 18 months.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 13 Feb 2017 DCO; up to a maximum of approximately 3 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.

TTDM 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 or proven by biopsy. TTDM was calculated using the Kaplan-Meier technique.

Time frame: Tumor scans performed at baseline then every ~8 weeks up to 48 weeks, then every ~ 12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.

Global health status/HRQoL was assessed using the EORTC QLQ-C30 global QoL scale which includes 2 items from the QLQ-C30: How would you rate your overall health during the past week? (Item 29) and How would you rate your overall QoL during the past week? (Item 30). Scores from 0 to 100 were derived for each item with higher scores indicating a better health status. Time to deterioration for global health status/HRQoL was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in global health status/HRQoL from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful deterioration. Time to deterioration was calculated using the Kaplan-Meier technique.

Time frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis. Only patients with baseline scores ≥ 10 were included in the analysis.

The EORTC QLQ-LC13 is a lung cancer specific module from the EORTC comprising 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, chest pain, arm/shoulder pain, and other pain), treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication. Scores from 0 to 100 were derived for each symptom item with higher scores representing greater symptom severity. Time to symptom deterioration was defined as time from randomization until the date of first clinically meaningful symptom deterioration (an increase in the score from baseline of ≥10) or death (by any cause) in the absence of a clinically meaningful symptom deterioration. Results are presented for time to deterioration in the following PRO endpoints identified as primary for EORTC QLQ-LC13: dyspnea, cough, hemoptysis and chest pain. Time to deterioration was calculated using the Kaplan-Meier technique.

Time frame: At baseline, every 4 weeks for first 8 weeks, then every ~8 weeks until 48 weeks, then every ~12 weeks thereafter until confirmed disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis. Only patients with baseline scores ≤ 90 were included in the analysis.

PFS2 was defined as the time from randomization to the time of the second progression or death. The date of second progression was recorded by the investigator and defined according to local standard clinical practice, and could have involved any of the following: objective radiological, symptomatic progression, or death. RECIST assessments were not collected for assessment of PFS2. PFS2 was calculated using the Kaplan-Meier technique.

Time frame: Following confirmed progression, patients were assessed every ~12 weeks until second disease progression. Assessed until 22 Mar 2018 DCO; up to a maximum of approximately 4 years.

Population: FAS included all randomized patients, analyzed on an ITT basis.