This study will assess the efficacy and safety of the combination of ceralasertib and durvalumab versus standard of care docetaxel in patients with locally advanced and metastatic NSCLC after progression on prior anti-PD-(L)1 therapy and platinum-based chemotherapy.
This study will consist of two treatment arms (Groups A and B). Participants will be randomised in a 1:1 ratio to one of the two treatment groups: * Group A: Ceralasertib plus durvalumab combination therapy Each 28-day cycle will begin with ceralasertib administered orally followed by durvalumab administered intravenously. * Group B: Docetaxel monotherapy Each 21-day cycle will begin with the administration of docetaxel.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
594
Participants will receive ceralasertib oral tablets.
Participants will receive durvalumab as an intravenous infusion.
Participants will received docetaxel as an intravenous infusion.
Overall Survival (OS)
The superiority of ceralasertib plus durvalumab combination therapy relative to docetaxel will be demonstrated by assessment of OS (HR with 95% CI and p-value) in participants with advanced NSCLC after second- or third-line therapy and without actionable genomic alterations. OS is defined as time from randomisation until the date of death due to any cause.
Time frame: Every 3 months (± 1 week) following objective progression of disease (PD) or treatment discontinuation (up to three years)
Progression-Free Survival (PFS)
PFS will be defined as the time from the date of randomisation until the date of objective PD.
Time frame: Up to 3 years
Objective Response Rate (ORR)
ORR is defined as the proportion of participant who have a Complete Response (CR) or Partial Response (PR) per RECIST 1.1.
Time frame: Up to 3 years
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1.
Time frame: Up to 3 years
Time To Response (TTR)
TTR is defined as the time from randomisation until the date of first documented objective response.
Time frame: Up to 3 years
Disease Control Rate (DCR)
DCR at 18 weeks is defined as the percentage of participants who have a CR or PR or who have stable disease (SD) for at least 17 weeks.
Time frame: At Week 18
Time to second progression or death (PFS2)
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Research Site
Mobile, Alabama, United States
Research Site
Chandler, Arizona, United States
Research Site
Los Alamitos, California, United States
Research Site
Los Angeles, California, United States
Research Site
Whittier, California, United States
Research Site
Jacksonville, Florida, United States
Research Site
Orlando, Florida, United States
Research Site
Tampa, Florida, United States
Research Site
Athens, Georgia, United States
Research Site
Atlanta, Georgia, United States
...and 183 more locations
Time from randomisation to PFS2 will be defined as the time from the randomisation to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy or death.
Time frame: Up to 3 years
Overall Survival (OS) at 12 months
OS is defined as time from randomisation until the data of death due to any cause.
Time frame: At 12 months
Time To Deterioration (TTD) of health-related quality of life (QoL)
TTD is defined as the time from randomisation until the date of first confirmed deterioration.
Time frame: Up to 3 years
TTD of physical function
TTD in physical functioning is measured by the EORTC QLQ-C30 Physical Function subscale of the EORTC QLQ-C30.
Time frame: Up to 3 years
Plasma concentrations for ceralasertib plus durvalumab combination therapy
The PK plasma concentration of ceralasertib when administered in combination with durvalumab will be assessed.
Time frame: Up to 3 years
Number of participants with Adverse Evens (AEs)
The safety and tolerability of ceralasertib plus durvalumab combination therapy as compared with docetaxel will be assessed.
Time frame: Up to 3 years