This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who are deemed to be ineligible for chemotherapy per Investigator assessment. Patients will be enrolled into 2 cohorts according to radiotherapy pretreatment dose (Cohort A: standard radiation therapy \[60 gray (Gy) ± 10% or hypofractionated bioequivalent dose (BED)\]; Cohort B: palliative radiation therapy \[40 to \< 54 Gy or hypofractionated BED\])
This is a Phase II open-label, single-arm, multicenter, international study to evaluate the clinical activity of durvalumab in patients with Stage III unresectable NSCLC who have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2 and who were treated with radiotherapy but are ineligible for chemotherapy. Patients will be enrolled into 2 cohorts according to the dose of radiotherapy received prior to study entry (Cohort A: Standard Radiotherapy \[60 Gy ± 10% or hypofractionated BED\]; Cohort B: Palliative Radiotherapy \[40 to \< 54 Gy or hypofractionated BED\]). Patients must not have progressed following radiation therapy, and radiation therapy must be completed within 6 weeks (42 days) prior to first study drug administration. The last dose of radiation therapy is defined as the day of the last radiation treatment session. All patients will receive 1500 mg durvalumab via IV infusion every 4 weeks (q4w) for up to a maximum of 12 months (up to 13 doses/cycles)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
102
All patients will receive 1500 mg durvalumab via IV infusion q4w for up to a maximum of 12 months.
Research Site
Number of Patients With Grade 3 and Grade 4 Possibly-related Adverse Events (PRAEs)
The safety and tolerability profile of durvalumab as defined by Grade 3 and Grade 4 PRAEs within 6 months from the initiation of durvalumab treatment. A PRAE was any TEAE with a possible relatedness to durvalumab, or where the relatedness was missing. If relatedness of a TEAE was missing at the primary DCO (30 March 2023) the TEAE was considered a PRAE.
Time frame: From first dose of durvalumab treatment until 6 months after initiation of durvalumab treatment
Median Progression-free Survival (mPFS)
Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time frame: From the first date of treatment until the date of objective disease progression or death or data cut-off date (36 months)
Progression-free Survival at 6 Months (PFS6)
Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time frame: From the first date of treatment until the date of objective disease progression or death (6 months)
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Tucson, Arizona, United States
Research Site
Tampa, Florida, United States
Research Site
Royal Oak, Michigan, United States
Research Site
Limoges, France
Research Site
Marseille, France
Research Site
Montpellier, France
Research Site
Nîmes, France
Research Site
Rouen, France
Research Site
Brescia, Italy
Research Site
Florence, Italy
...and 25 more locations
Progression-free Survival at 12 Months (PFS12)
Progression-free survival is defined as the time from the date of first dose of durvalumab until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient discontinues durvalumab or receives another anticancer therapy prior to progression according to RECIST 1.1 as assessed by the Investigator. Patients who had not progressed or died at the time of analysis were censored at the date of their last evaluable tumor assessment. If a patient progressed or died after two or more missed visits, they were censored at the date of the latest evaluable assessment prior to the missed visits.
Time frame: From the first date of treatment until the date of objective disease progression or death (12 months)
Median Overall Survival (mOS)
The OS is defined as the time from the date of first dose of durvalumab until death due to any cause. Patients who were not known to have died at the time of analysis were censored at the last recorded date when they were known to have been alive.
Time frame: From the first date of treatment until death or data cut-off due to any cause (36 months)
Overall Survival at 12 Months (OS12)
The OS is defined as the time from the date of first dose of durvalumab until death due to any cause. Patients who were not known to have died at the time of analysis were censored at the last recorded date when they were known to have been alive.
Time frame: From the first date of treatment until death due to any cause (12 months)
Objective Response Rate (ORR)
The ORR is the proportion (%) of patients with an overall response of complete response (CR) or partial response (PR) (confirmed by a follow-up scan at least 4 weeks after showing CR or PR) per RECIST 1.1 criteria. CR is disappearance of all target lesions (TLs) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \< 10 mm. PR is at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months)
Duration of Response (DoR)
The DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until the first date of documented progression per RECIST1.1 or death in the absence of disease progression.
Time frame: From 8 weeks ±1 week after durvalumab treatment initiation and continue every 8 weeks (q8w) ±1 week through 48 weeks and every 12 weeks (q12w) ±1 week until disease progression or data cut-off (36 months)
Lung Cancer Mortality
The lung cancer mortality (NSCLC-related death) is assessed using the deaths which are reported as 'NSCLC-related' and is defined as the time (days) from the date of first dose of durvalumab until date of death due to lung cancer.
Time frame: From date of treatment start until death due to lung cancer (36 months)
Number of Patients With Events (AEs)
The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed.
Time frame: From screening (Day -28) till data cut-off (36 months)
Number of Patients With Adverse Events of Special Interests (AESIs)
The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed. An AESI is an AE of scientific and medical interest specific to the understanding of durvalumab. AESIs for durvalumab include, but are not limited to, events with a potential inflammatory or immune-mediated mechanism and which may require more frequent monitoring and/or interventions such as steroids, immunosuppressants and/or hormone replacement therapy. Here, number of patients experienced AESIs are presented. Serious adverse event of special interests (SAESIs).
Time frame: From screening (Day -28) till data cut-off (36 months)
Number of Patients With Immune-mediated Adverse Events (imAEs)
The safety and tolerability profile of durvalumab treatment, including all adverse events (AEs) was assessed. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action and where there is no clear alternate etiology. Here, number of patients experienced imAEs are presented. Immune-mediated serious adverse events (imSAEs)
Time frame: From screening (Day -28) till data cut-off (36 months)