This is a Phase III, randomized, placebo-controlled, double-blind, multi-center study assessing the efficacy and safety of durvalumab with SoC SBRT versus placebo with SoC SBRT in patients with unresected clinical Stage I/II lymph node-negative (T1 to T3N0M0) NSCLC. An additional cohort will assess Osimertinib following SBRT in patients with early stage unresected T1 to T3N0M0 NSCLC harbouring an EGFR mutation.
Patients with Stage I/II lymph node negative NSCLC and confirmed to meet all eligibility criteria will be randomized 1:1 to receive either Durvalumab + SoC SBRT or placebo + SoC SBRT. The primary objective of main cohort is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of PFS. Key secondary is to assess the efficacy of Durvalumab with SoC SBRT compared to placebo with SoC SBRT in terms of Overall Survival (OS). In addition, a study cohort with a sufficient number of patients harboring an EGFR-TKI sensitizing mutation, will receive Osimertinib treatment after completion of SoC SBRT as definitive treatment of Stage I/II lymph node-negative NSCLC. The primary objective of Osimertinib cohort is to assess efficacy of Osimertinib following SoC SBRT in terms of 4-year PFS. Key secondary objectives include safety, OS and efficacy of Osimertininb treatment with SBRT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
724
Durvalumab 1500 mg every 4 weeks \[q4w\] intravenously \[iv\] for up to 26 cycles or until progression or other discontinuation criteria are met.
Matching placebo for infusion every 4 weeks iv for up to 26 cycles or until progression or other discontinuation criteria are met.
Osimertinib 80 mg every day \[qd\] orally for up to 36 months or until progression or other discontinuation criteria are met. Osimertinib treatment should start from 7 to 14 days after completion of SBRT
Research Site
Tuscaloosa, Alabama, United States
Research Site
Chandler, Arizona, United States
Research Site
Phoenix, Arizona, United States
Research Site
Tucson, Arizona, United States
Research Site
Duarte, California, United States
Research Site
Progression-Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1 in subpopulation of patients with Stage I/II NSCLC
Main Cohort
Time frame: from randomization up to 6 years
4-year Progression-Free Survival (4y-PFS) by ICR according to RECIST 1.1 criteria
Osimertinib Cohort
Time frame: from treatment start up to 5 years
Progression-Free Survival (PFS) assessed by BICR per RECIST 1.1 in all randomised patients with Stage I/II NSCLC
Main Cohort
Time frame: from randomization up to 6 years
Overall Survival (OS)
Main Cohort
Time frame: from randomization up to 7 years
Concentration of durvalumab in serum such as peak concentration and trough
Main Cohort
Time frame: 12 weeks after last dose
Detection of ADA neutralising antibodies titers
Main Cohort
Time frame: up to 6 months after last dose
Health-related quality of life in patients treated with durvalumab with SoC SBRT compared to placebo with SoC SBRT using the EORTC QLQ-C30
Main Cohort
Time frame: from randomization up to 7 years
Proportion of patients alive and progression free at 24 months from randomisation (PFS24) assessed by BICR according to RECIST 1.1
Main Cohort
Time frame: at 24 months following randomization
Time to progression (TTP) assessed by BICR according to RECIST 1.1
Main Cohort
Time frame: from randomization up to 6 years
Time to death or distant metastasis (TTDM) assessed by BICR according to RECIST 1.1
Main Cohort
Time frame: from randomization up to 6 years
Time from randomisation to second progression (PFS2) as defined by local standard clinical practice
Main Cohort
Time frame: from randomization up to 7 years
Assessment of AEs by CTCAE v 5.0 as measures of the safety and tolerability of Durvalumab with SoC SBRT compared to placebo with SoC SBRT
Main Cohort
Time frame: up to 3 months after last dose
Assessment of AEs by CTCAE v 5.0 as measures of the safety, tolerability and compliance of osimertinib with SoC SBRT therapy
Osimertinib Cohort
Time frame: Up to 35 days after last dose
WHO performance status
Osimertinib Cohort
Time frame: from treatment start up to 5 years
ECG QT interval
Osimertinib Cohort
Time frame: Up to 156 weeks of treatment or treatment discontinuation
Overall Survival
Osimertinib Cohort
Time frame: from treatment start up to 5 years
Time To Progression (TTP)
Osimertinib Cohort
Time frame: from treatment start up to 5 years
Time to CNS progression
Osimertinib Cohort
Time frame: from treatment start up to 5 years
PFS2
Osimertinib Cohort
Time frame: from treatment start up to 5 years
Site(s) of disease progression
Osimertinib Cohort
Time frame: from treatment start up to 5 years
PFS by ICR using RECIST 1.1
Osimertinib Cohort
Time frame: from treatment start up to 5 years
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Long Beach, California, United States
Research Site
Los Angeles, California, United States
Research Site
San Diego, California, United States
Research Site
Newark, Delaware, United States
Research Site
Washington D.C., District of Columbia, United States
...and 199 more locations