A global study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable Epidermal Growth Factor Receptor Mutation Positive non-small cell lung cancer
This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of osimertinib following chemoradiation in patients with stage III unresectable EGFR mutation-positive NSCLC, including the most common EGFR sensitising mutations (Ex19Del and L858R), either alone or in combination with other EGFR mutations. Chemoradiation may have been given either given concurrently or sequentially. Patients whose disease has not progressed following chemoradiation will be randomised within 6 weeks of completion of chemoradiation to receive osimertinib or placebo in a 2:1 ratio, and treatment will be continued until disease progression, unacceptable toxicity or other discontinuation criteria are met. After progression, patients can be unblinded and may receive open-label osimertinib. After the final OS analysis, the study blind will be broken and patients still receiving open-label osimertinib will be supplied with open-label osimertinib by AstraZeneca for as long as their treating physician considers they are deriving clinical benefit.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
216
The initial dose of Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.
The initial dose of Placebo Osimertinib 80mg once daily can be reduced to 40mg once daily. Treatment can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met
Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)
Time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation
Number of PFS events (PFS is time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on BICR assessment according to RECIST v1.1)
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA
Number of PFS events (PFS is time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on blinded independent central review (BICR) assessment according to RECIST v1.1)
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)
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Research Site
Duarte, California, United States
Research Site
Atlanta, Georgia, United States
Research Site
Florham Park, New Jersey, United States
Research Site
Salt Lake City, Utah, United States
Research Site
Madison, Wisconsin, United States
Research Site
Ciudad Autónoma de Bs. As., Argentina
Research Site
Ciudad Autónoma de Bs. As., Argentina
Research Site
Mar del Plata, Argentina
Research Site
Rosario, Argentina
Research Site
San Salvador de Jujuy, Argentina
...and 108 more locations
Time from randomisation until the date of CNS disease progression or death (by any cause in the absence of CNS progression) regardless of whether the patient withdraws from randomised therapy or receives another anti-cancer therapy prior to progression, based on CNS BICR assessment according to RECIST v1.1
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Overall Survival (Count)
Number of patients with Overall Survival (OS), the time from the date of randomisation until date of death by any cause
Time frame: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
Overall Survival (Duration)
Time from the date of randomisation until death by any cause
Time frame: Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
Objective Response Rate by Blinded Independent Central Review (BICR)
Percentage of evaluable patients with at least one BICR assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target lesions (TL) since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis to \<10mm. PR defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline sum of diameters). Responses include both confirmed and unconfirmed BICR responses
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR)
Date of PFS event - date of first unconfirmed response + 1 day (and expressed in months) for unconfirmed responses only
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Disease Control Rate by Blinded Independent Central Review (BICR)
Percentage of patients who have a best overall response of complete response (CR), partial response (PR) or stable disease (SD) as assessed by BICR
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Tumour Shrinkage by Blinded Independent Central Review (BICR)
Depth of response (or tumour shrinkage or change in tumour size) was assessed using BICR responses in target lesions. The best change in tumour size is the largest decrease from baseline or the smallest increase from baseline in the absence of a reduction
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR)
Proportion with depth of response (or tumour shrinkage or change in tumour size)
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks until BICR-confirmed radiological disease progression. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Time to Death or Distant Metastases by Blinded Independent Central Review (BICR)
Time from the date of randomisation until the first date of distant metastases or date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is detected on a scan that is anywhere other than lung or regional lymph node according to RECIST v1.1 or proven by biopsy
Time frame: Time from randomisation to the date of distant metastases or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Time to Study Treatment Discontinuation
Time from randomisation to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death (i.e. date of study treatment discontinuation/death or censoring - date of randomisation + 1 day, expressed in months)
Time frame: Time from randomisation to the earlier of the date of study treatment discontinuation or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Time to First Subsequent Treatment
Time from the date of randomisation to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death
Time frame: Time from randomisation to the start of first subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Time to Second Subsequent Treatment
Time from the date of randomisation to the earlier of the second subsequent anti-cancer therapy start date following study drug discontinuation or death
Time frame: Time from randomisation to the start of second subsequent anti-cancer therapy or death. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months
Second Progression-free Survival (PFS2)
Time from randomisation to the earliest progression event following first objective disease progression, subsequent to the first subsequent therapy, or death.
Time frame: Every 8 weeks for first 48 weeks, then every 12 weeks. Assessed up to date of DCO (05Jan24) to a maximum of approximately 63 months