NCT03521154 · CITED IN SOURCE DOCUMENTS

A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-08-04

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)

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outcome · POSTED

Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation

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outcome · POSTED

Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA

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outcome · POSTED

Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (BICR)

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outcome · POSTED

Overall Survival (Count)

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outcome · POSTED

Overall Survival (Duration)

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outcome · POSTED

Objective Response Rate by Blinded Independent Central Review (BICR)

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outcome · POSTED

Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR)

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outcome · POSTED

Disease Control Rate by Blinded Independent Central Review (BICR)

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outcome · POSTED

Tumour Shrinkage by Blinded Independent Central Review (BICR)

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outcome · POSTED

Proportion With Tumour Shrinkage by Blinded Independent Central Review (BICR)

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outcome · POSTED

Time to Death or Distant Metastases by Blinded Independent Central Review (BICR)

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outcome · POSTED

Time to Study Treatment Discontinuation

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outcome · POSTED

Time to First Subsequent Treatment

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outcome · POSTED

Time to Second Subsequent Treatment

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outcome · POSTED

Second Progression-free Survival (PFS2)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria 1. Male or female aged at least 18 years. 2. Patients with histologically documented NSCLC of predominantly non-squamous Pathology who present with locally advanced, unresectable (Stage III) disease (according to Version 8 of the International Association for the Study of Lung Cancer \[IASLC\] Staging Manual in Thoracic Oncology). 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 cobas® EGFR Mutation Test v2 (Roche Diagnostics) or FoundationOne® test in a CLIA certified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central testing (cobas® v2 only). 4. Patients must have received either concurrent chemoradiation or sequential chemoradiation including at least 2 cycles of platinum based chemotherapy and a total dose of radiation of 60 Gy ±10% (54 to 66 Gy). 5. Chemoradiation must be completed ≤6 weeks prior to randomization. 6. Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy. 7. World Health Organization (WHO) performance status of 0 or 1. 8. Life expectancy \>12 weeks at Day 1. 9. Female patients who are not abstinent (in line with the preferred and usual lifestyle choice) must be using adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug; or female patients must have an evidence of non-childbearing potential. Exclusion Criteria 1. Mixed small cell and non-small cell lung cancer histology 2. History of interstitial lung disease (ILD) prior to chemoradiation 3. Symptomatic pneumonitis following chemoradiation 4. Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) \> Grade 2 from the prior chemoradiation therapy 5. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 ECGs * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG * Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes 6. Inadequate bone marrow reserve or organ function 7. History of other malignancies, except: adequately treated non-melanoma skin cancer or lentigo maligna , curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for \> 5 years following the end of treatment and which, in the opinion of the treating physician, do not have a substantial risk of recurrence of the prior malignancy. 8. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). 9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of osimertinib 10. Prior treatment with any prior chemotherapy, radiation therapy, immunotherapy or investigational agents for NSCLC outside of that received in the definitive setting for Stage III disease (chemotherapy and radiotherapy in SCRT and CCRT regimens is allowed for treatment of Stage III disease). 11. Prior treatment with EGFR-TKI therapy 12. Major surgery as defined by the investigator within 4 weeks of the first dose of study drug. 13. Patients currently receiving (unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be strong inducers of CYP3A4 (at least 3 weeks prior to receiving the first dose of study drug). 14. Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal implants, intracranial surgical clips and metal foreign bodies
healthy Volunteers: false
maximum Age: 130 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.
intervention Names
Drug: Osimertinib 80mg/40mg
label
Osimertinib
type
EXPERIMENTAL
description
Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule
intervention Names
Drug: Placebo Osimertinib 80mg/40mg
label
Placebo Osimertinib
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Osimertinib
description
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.
name
Osimertinib 80mg/40mg
type
DRUG
arm Group Labels
Placebo Osimertinib
description
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
name
Placebo Osimertinib 80mg/40mg
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 216
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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
measure
Progression-free Survival (PFS) by Blinded Independent Central Review (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

secondary Outcomes

description
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)
measure
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Ex19del or L858R Mutation
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
description
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)
measure
Number of Participants With Progression-free Survival (PFS) Events in Patients With EGFR Mutations Ex19del or L858R Detectable in Plasma-derived ctDNA
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
description
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
measure
Central Nervous System (CNS) Progression-free Survival (PFS) by Blinded Independent Central Review (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
description
Number of patients with Overall Survival (OS), the time from the date of randomisation until date of death by any cause
measure
Overall Survival (Count)
time Frame
Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
description
Time from the date of randomisation until death by any cause
measure
Overall Survival (Duration)
time Frame
Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months
description
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
measure
Objective Response Rate by Blinded Independent Central Review (BICR)
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
description
Date of PFS event - date of first unconfirmed response + 1 day (and expressed in months) for unconfirmed responses only
measure
Duration of Response, Unconfirmed by Blinded Independent Central Review (BICR)
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
description
Percentage of patients who have a best overall response of complete response (CR), partial response (PR) or stable disease (SD) as assessed by BICR
measure
Disease Control Rate by Blinded Independent Central Review (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
description
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
measure
Tumour Shrinkage by Blinded Independent Central Review (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
description
Proportion with depth of response (or tumour shrinkage or change in tumour size)
measure
Proportion With Tumour Shrinkage by Blinded Independent Central Review (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
description
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
measure
Time to Death or Distant Metastases by Blinded Independent Central Review (BICR)
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
description
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)
measure
Time to Study Treatment Discontinuation
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

Full study description

brief Summary: 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
detailed Description: 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.

Source references

references

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