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
Name: Osimertinib 80mg/40mg
Name: Placebo Osimertinib 80mg/40mg
Description: Defined as the 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 assessment according to RECIST 1.1
Measure: Progression-free survival (PFS) Time: Approximately 13 monthsDescription: Defined as the 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 assessment according to RECIST 1.1
Measure: PFS in patients with EGFR Ex19del or L858R mutation Time: Approximately 13 monthsDescription: Defined as the 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 assessment according to RECIST 1.1
Measure: PFS in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA Time: Approximately 13 monthsDescription: Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1
Measure: Time to CNS PFS Time: Approximately 13 monthsDescription: Defined as the time from randomization until death from any cause
Measure: Overall survival (OS) Time: Approximately 45 monthsDescription: Defined as the number (%) of patients with measurable disease with at least 1 visit response of CR (Complete response) or PR (Partial response) based on blinded independent central review assessment according to RECIST 1.1
Measure: Objective response rate (ORR) Time: Approximately 13 monthsDescription: Defined as the time from the date of first documented response (i.e., subsequently confirmed) until the date of documented progression or death in the absence of disease progression based on blinded independent central review assessment according to RECIST 1.1
Measure: Duration of response (DoR) Time: Approximately 13 monthsDescription: Defined as Disease control rate is defined as the percentage of subjects who have a best overall response of CR or PR or SD based on blinded independent central review assessment according to RECIST 1.1
Measure: Disease control rate (DCR) Time: Approximately 13 monthsDescription: Defined as the relative change in the sum of the longest diameters of RECIST target lesions at the nadir in the absence of new lesions or progression of non-target lesions compared to baseline based on blinded independent central review assessment according to RECIST 1.1
Measure: Tumor shrinkage Time: Approximately 13 monthsDescription: Defined as the time from the date of randomization until the first date of distant metastasis or date of death in the absence of distant metastasis based on blinded independent central review assessment according to RECIST 1.1
Measure: Time to death or distant metastases (TTDM) Time: Approximately 13 monthsDescription: Defined as the time from randomization to the earlier of the date of study treatment discontinuation (regardless of the reason for study treatment discontinuation) or death
Measure: Time to treatment discontinuation Time: Approximately 13 monthsDescription: Time from randomisation to second progression (PFS2) is defined as the time from the date of randomisation to the earliest of the progression event subsequent to that used for the primary variable PFS or date of death after starting subsequent anti-cancer treatment.
Measure: Second progression free survival on a subsequent treatment (PFS2) Time: Assessed by investigator in accordance with clinical practice-approximately 21 monthsDescription: Defined as the time from the date of randomization to the earlier of the date of anti-cancer therapy start date following study drug discontinuation or death
Measure: Time to first subsequent therapy (TFST) Time: Approximately 13 monthsDescription: Defined as the time from the date of randomization to the earlier of the date of second subsequent anti-cancer therapy start date following study drug discontinuation or death.
Measure: Time to second subsequent therapy (TSST) Time: Approximately 21 monthsDescription: Change in symptoms from baseline
Measure: Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires Time: Approximately 21 monthsDescription: AEs graded by CTCAE version 5.0
Measure: Incidence of Adverse Events (AEs) Time: Approximately 14 monthsDescription: The pharmacokinetics exposure parameters derived from plasma concentrations of osimertinib and AZD5104
Measure: Plasma concentrations of osimertinib and AZD5104 Time: Trough concentrations at Week 4,12 and 24Allocation: Randomized
Parallel Assignment
There is one SNP
PFS in patients with EGFR Ex19del or L858R mutation. --- L858R ---
PFS in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA. --- L858R ---
3. The tumor harbours one of the two common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations, assessed by cobasĀ® EGFR Mutation Test v2 (Roche Diagnostics) in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing. --- L858R ---
Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies Non Small Cell Lung Cancer (Stage III) Lung Neoplasms Carcinoma, Non-Small-Cell Lung 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. --- L858R ---