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Clinical Trials List

Protocol NumberD5160C00048
NCT Number(ClinicalTrials.gov Identfier)NCT03521154
Active

2018-06-01 - 2027-12-31

Phase III

Recruiting8

ICD-10C33

Malignant neoplasm of trachea

ICD-10Z51.12

Encounter for antineoplastic immunotherapy

ICD-9162.0

Malignant neoplasm of trachea

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter, International Study of Osimertinib as Maintenance Therapy in Patients With Locally Advanced, Unresectable EGFR Mutation-positive Non-Small Cell Lung Cancer (Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy (LAURA).

  • Trial Applicant

  • Sponsor

    AstraZeneca

  • Trial scale

    Multi-Regional Multi-Center

  • Update

    2026/02/01

Investigators and Locations

Principal Investigator
Taichung Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chih-Liang Wang Division of Hematology & Oncology
Linkou Chang Gung Medical Foundation

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Te-Chun Hsia Division of Thoracic Medicine
China Medical University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator James Chih-Hsin Yang Division of Hematology & Oncology
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Yuh-Min Chen Division of Hematology & Oncology
Taipei Veterans General Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator 吳銘芳 Division of General Internal Medicine
Chung Shan Medical University Hospital

Co-Principal Investigator

  • 吳子卿 Division of General Internal Medicine
  • 曹世明 Division of General Internal Medicine

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator Chien-Chung Lin Division of General Internal Medicine
National Taiwan University Hospital

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Principal Investigator CHIN-CHOU WANG Division of Thoracic Medicine
Kaoshiung Chang Gung Memorial Hospital of the C.G.M.F.

Co-Principal Investigator

The Actual Total Number of Participants Enrolled

0 Recruiting

Condition/Disease

Non Small Cell Lung Cancer

Objectives

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.

Test Drug

TAGRISSO

Active Ingredient

Osimertinib

Dosage Form

film-coated tablet

Dosage

40mg, 80mg

Endpoints

Primary Outcome Measures :
Progression-free survival (PFS) [ Time Frame: Approximately 13 months ]
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


Secondary Outcome Measures :
PFS in patients with EGFR Ex19del or L858R mutation [ Time Frame: Approximately 13 months ]
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

PFS in patients with EGFR mutations Ex19del or L858R detectable in plasma-derived ctDNA [ Time Frame: Approximately 13 months ]
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

Time to CNS PFS [ Time Frame: Approximately 13 months ]
Defined as earlier event of CNS progression or death based on blinded independent central review assessment according to RECIST 1.1

Overall survival (OS) [ Time Frame: Approximately 45 months ]
Defined as the time from randomization until death from any cause

Objective response rate (ORR) [ Time Frame: Approximately 13 months ]
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

Duration of response (DoR) [ Time Frame: Approximately 13 months ]
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

Disease control rate (DCR) [ Time Frame: Approximately 13 months ]
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

Tumor shrinkage [ Time Frame: Approximately 13 months ]
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

Time to death or distant metastases (TTDM) [ Time Frame: Approximately 13 months ]
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

Time to treatment discontinuation [ Time Frame: Approximately 13 months ]
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

Second progression free survival on a subsequent treatment (PFS2) [ Time Frame: Approximately 13 months ]
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.

Time to first subsequent therapy (TFST) [ Time Frame: Approximately 13 months ]
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

Time to second subsequent therapy (TSST) [ Time Frame: Approximately 21 months ]
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.

Patients reported disease-related symptoms and HRQoL by EORTC QLQ-LC13 and EORTC QLQ-30 questionnaires [ Time Frame: Approximately 21 months ]
Change in symptoms from baseline

Incidence of Adverse Events (AEs) [ Time Frame: Approximately 13 months ]
AEs graded by CTCAE version 5.0

Plasma concentrations of osimertinib and AZD5104 [ Time Frame: Trough concentrations at Week 4,12 and 24 ]
The pharmacokinetics exposure parameters derived from plasma concentrations of osimertinib and AZD5104

Inclution Criteria

Inclusion criteria
Part I Screening
Part I screening applies only to patients that do not have a pre-existing local positive (Exon 19
deletion or L858R) cobas® EGFR Mutation Test v2 (Roche Diagnostics) in a CLIA-certified
(USA sites) or an accredited local laboratory (sites outside of the USA) conducted according
to the cobas® EGFR Mutation Test v2 instructions for use.
Patients are eligible to be included in the study only if all of the following inclusion criteria
apply and none of the Part II screening exclusion criteria numbers 1, 2, 7, 9-11 and 15-20
apply:
Informed consent
1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this protocol
2. Provision of signed and dated written informed consent for Part I screening form prior to
any mandatory provision of tumor samples for testing of EGFR mutation status.
The ICF process is described in Appendix A 3.
Age and Sex
3. Male and Female patient must be aged at least 18 years. Patients from Japan aged at least
20 years.
Type of patient and disease characteristics
4. 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).
It is recommended but not required that except for overt cT4 disease, nodal status N2
or N3 should have been proven by biopsy, via endobronchial ultrasound,
mediastinoscopy, or thoracoscopy or in absence of biopsy, should have been
confirmed with whole body 18F-fluoro-deoxyglucose positron emission tomography
(PET) plus contrast-enhanced computed tomography (CT) in addition to or in
combination with PET
5. Patient who can provide an unstained archived formalin-fixed paraffin embedded tumor
tissue sample in a quantity sufficient to allow for prospective central analysis of EGFR
mutation status.
Further information is provided in section 8.1.1 and in the laboratory manual.
Part II Screening
Part II screening applies to: (i) patients that have a pre-existing local positive (Exon 19
Deletion or L858R) cobas® EGFR Mutation Test v2 (Roche Diagnostics) in a CLIA-certified
(USA sites) or an accredited local laboratory (sites outside of the USA) conducted according
to the cobas® EGFR Mutation Test v2 instructions for use or (ii) patients who completed Part
I screening and have centrally confirmed EGFR mutation (Ex19 Deletion or L858R) positive
NSCLC.
Patients are eligible to be included in the study only if all of the following inclusion criteria
and none of the exclusion criteria apply:
Informed consent
1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Provision of signed and dated, written informed consent form for the main study prior to
any mandatory study specific procedures, sampling, and analyses.
3. Provision of signed and dated written genetic informed consent prior to collection of sample
for genetic analysis for inclusion in the optional genetic research.
Note: If a patient declines to participate in any voluntary exploratory research and/or genetic
component of the study for optional test, there will be no penalty or loss of benefit to the
patient and he/she will not be excluded from other aspects of the study.
Age and Sex
4. Male and Female patient must be aged at least 18 years. Patients from Japan aged at least
20 years.
Type of patient and disease characteristics
5. 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)
It is recommended but not required that except for overt cT4 disease, nodal status N2
or N3 should have been proven by biopsy, via endobronchial ultrasound,
mediastinoscopy, or thoracoscopy or in absence of biopsy, should have been
confirmed with whole body 18F-fluoro-deoxyglucose positron emission tomography
(PET) plus contrast-enhanced computed tomography (CT) in addition to or in
combination with PET
*Patients with a stage III tumor of squamous histology who have a pre-existing local
positive test (Exon 19 Deletion or L858R) assessed with cobas® EGFR Mutation Test
v2 are eligible.
6. 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) in a CLIAcertified (USA sites) or an accredited local laboratory (sites outside of the USA) or by central
testing.
7. Patients must not have had disease progression during or following definitive platinumbased, chemoradiation therapy.
8. Patients must have received either concurrent chemoradiation or sequential chemoradiation
regimens as defined below:
CCRT- Patients must have received at least 2 cycles of platinum-based chemotherapy (or
5 doses of weekly platinum–based chemotherapy) concurrent with radiation therapy, which
must be completed ≤6 weeks prior to randomization. The final chemotherapy cycle must end
prior to, or concurrently with, the final dose of radiation. (A final cycle of platinum and
pemetrexed doublet is permitted up to 3 days after the last dose of radiation). Consolidation chemotherapy after radiation is not permitted but administration of chemotherapy prior to
CCRT is permitted.
SCRT- SCRT is defined as chemotherapy followed by radiation therapy and not radiation
therapy followed by chemotherapy. Patients must have received at least 2 cycles of platinumbased chemotherapy prior to radiation treatment, which must be completed ≤6 weeks prior to
randomization. Consolidation chemotherapy after radiation is not permitted
If a patient has received at least 2 cycles of platinum-based chemotherapy and subsequently
receives one cycle of platinum-based chemotherapy or < 5 doses of weekly platinum–based
chemotherapy concurrent with radiation therapy, this will be considered SCRT
If a patient has received 1 cycle of platinum-based chemotherapy and subsequently receives
one cycle of platinum-based chemotherapy or < 5 doses of weekly platinum–based
chemotherapy concurrent with radiation therapy, this will not be considered CCRT or SCRT
and the patient will not be eligible
9. The platinum-based chemotherapy regimen must contain one of the following agents:
etoposide, vinblastine, vinorelbine, paclitaxel, docetaxel, or pemetrexed, according to the local
standard of care regimens. Gemcitabine is permitted if used prior to radiation but not with
radiation.
Where possible, chemotherapy regimens should be given according to National
Comprehensive Cancer Network or European Society for Medical Oncology guidelines
10. Patients must have received a total dose of radiation of 60 Gy ±10% (54 to 66 Gy) as part
of the chemoradiation therapy in order to be randomized. It is recommended but not required
that patients eligible for randomization have a
• Mean lung dose <20 Gy and/or V20 <35%
• Mean esophagus dose <34 Gy
• Heart V50 <25%, V30 <50%, and V45 <35%
11. World Health Organization (WHO) performance status of 0 or 1 at Part II screening and
Day 1
12. Life expectancy >12 weeks at Day 1
Reproduction
13. Female patients who are not abstinent (in line with the preferred and usual lifestyle choice
of the patient) and intend to be sexually active with a male partner 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 by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrhoeic for at least 12
months following cessation of all exogenous hormonal treatments
• Female patients less than 50 years old would be consider postmenopausal if they have
been amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatments and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
levels in the post-menopausal range for the institution
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral
oophorectomy, or bilateral salpingectomy but not tubal ligation
14. Male patients must be willing to use barrier contraception, i.e., condoms

Exclusion Criteria

Exclusion criteria
Part II Screening
Patients are eligible to be included in Part II screening process only if none of the exclusion
criteria apply:
Medical conditions
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. Patients with irreversible toxicity that is not
reasonably expected to be exacerbated by study drug may be included (e.g. hearing loss) after
consultation with the AstraZeneca medical monitor.
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, e.g., complete left bundle branch block, third-degree heart block, seconddegree heart block.
• 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-See section 6.5.2 for more details.
6. Inadequate bone marrow reserve or organ function as demonstrated by any of the following
laboratory values.
• Absolute neutrophil count <1.5 x 109
/L
• Platelet count <100 x 10
9
/L
• Haemoglobin <90 g/L
• Alanine aminotransferase (ALT) >2.5x the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) >2.5x ULN
• Total bilirubin >1.5x ULN or >3x ULN in the presence of documented Gilbert’s
Syndrome (unconjugated hyperbilirubinemia)
• Creatinine >1.5x ULN concurrent with creatinine clearance <50 mL/min (measured or
calculated by Cockcroft and Gault equation); confirmation of creatinine clearance is
only required when creatinine is >1.5xULN
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, which in the Investigator’s opinion makes it
undesirable for the patient to participate in the trial or which would jeopardise compliance
with the protocol; or active infection including hepatitis B, hepatitis C and human
immunodeficiency virus (HIV). Active infection will include any patients receiving
intravenous treatment for infection; active hepatitis B infection will, at a minimum, include all
patients who are hepatitis B surface antigen positive (HbsAg positive) based on serology
assessment. Screening for chronic conditions is not required.
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.
Prior/concomitant therapy
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). Prior surgical resection (i.e. stage I or II) is permitted.
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).
Prior/concurrent clinical study experience
14. Participation in another clinical study with an investigational product during the 4 weeks
prior to Day 1. Patients in the follow-up period of an interventional study are permitted.
Other exclusions
15. Patient with involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).
16. Judgment by the investigator that the patient should not participate in the study if the
patient is unlikely to comply with study procedures, restrictions and requirements.
17. Patient was previously randomized in the present study.
18. For female patients only - currently pregnant (confirmed with positive pregnancy test) or
breast-feeding.
19. Contraindication to MRI, including but not limited to, claustrophobia, pace makers, metal
implants, intracranial surgical clips and metal foreign bodies.
20. History of hypersensitive to active or inactive excipients of osimertinib or drugs with a
similar chemical structure or class to osimertinib.

The Estimated Number of Participants

  • Taiwan

    42 participants

  • Global

    200 participants

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