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

NCT ID: NCT03521154

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 216 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-19
• Study Completion Date: 2027-04-13

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.

Conditions

Non Small Cell Lung Cancer (Stage III)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Osimertinib

Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule.

Group Type: EXPERIMENTAL

Osimertinib 80mg/40mg

Intervention Type: DRUG

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.

Placebo Osimertinib

Matching placebo for Osimertinib (80mg or 40mg orally, once daily), in accordance with the randomization schedule

Group Type: PLACEBO_COMPARATOR

Placebo Osimertinib 80mg/40mg

Intervention Type: DRUG

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

Interventions

Osimertinib 80mg/40mg

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.

Intervention Type: DRUG

Placebo Osimertinib 80mg/40mg

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suresh S Ramalingam, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University School of Medicine, Atlanta, U.S.

Shun Lu, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Chest Hospital, Shanghai, China

Locations

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

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Rosario, , Argentina

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San Salvador de Jujuy, , Argentina

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Barretos, , Brazil

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Curitiba, , Brazil

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Florianópolis, , Brazil

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Fortaleza, , Brazil

Research Site

Porto Alegre, , Brazil

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Porto Alegre, , Brazil

Research Site

Ribeirão Preto, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

Research Site

Beijing, , China

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Beijing, , China

Research Site

Changchun, , China

Research Site

Changsha, , China

Research Site

Chengdu, , China

Research Site

Guangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Hangzhou, , China

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Jinan, , China

Research Site

Linhai, , China

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Shanghai, , China

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Shanghai, , China

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Ürümqi, , China

Research Site

Wuhan, , China

Research Site

Wuhan, , China

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Budapest, , Hungary

Research Site

Budapest, , Hungary

Research Site

Gyöngyös - Mátraháza, , Hungary

Research Site

Pécs, , Hungary

Research Site

Bangalore, , India

Research Site

Gurgaon, , India

Research Site

Hubli, , India

Research Site

Karamsad, , India

Research Site

Kolkata, , India

Research Site

Nashik, , India

Research Site

New Delhi, , India

Research Site

New Delhi, , India

Research Site

New Delhi, , India

Research Site

Hiroshima, , Japan

Research Site

Kanazawa, , Japan

Research Site

Kashiwa, , Japan

Research Site

Nagoya, , Japan

Research Site

Niigata, , Japan

Research Site

Osaka, , Japan

Research Site

Sakaishi, , Japan

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Sapporo, , Japan

Research Site

Sayama, , Japan

Research Site

Sendai, , Japan

Research Site

Shinjuku-ku, , Japan

Research Site

Sunto-gun, , Japan

Research Site

Yokohama, , Japan

Research Site

George Town, , Malaysia

Research Site

Kuala Lumpur, , Malaysia

Research Site

Kuala Selangor, , Malaysia

Research Site

Mérida, , Mexico

Research Site

Lima, , Peru

Research Site

Lima, , Peru

Research Site

Lima, , Peru

Research Site

Lima, , Peru

Research Site

San Isidro, , Peru

Research Site

Kazan', , Russia

Research Site

Kostroma, , Russia

Research Site

Moscow, , Russia

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Novisibirsk, , Russia

Research Site

Obninsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

Research Site

Ufa, , Russia

Research Site

Cheongju-si, , South Korea

Research Site

Incheon, , South Korea

Research Site

Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

Research Site

Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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San Sebastián, , Spain

Research Site

Seville, , Spain

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Valencia, , Spain

Research Site

Kaohsiung City, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Taichung, , Taiwan

Research Site

Tainan City, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taoyuan District, , Taiwan

Research Site

Bangkok, , Thailand

Research Site

Bangkok, , Thailand

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Bangkok, , Thailand

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Bangkok, , Thailand

Research Site

Hat Yai, , Thailand

Research Site

Khon Kaen, , Thailand

Research Site

Lampang, , Thailand

Research Site

Mueang, , Thailand

Research Site

Adana, , Turkey (Türkiye)

Research Site

Adapazarı, , Turkey (Türkiye)

Research Site

Ankara, , Turkey (Türkiye)

Research Site

Ankara, , Turkey (Türkiye)

Research Site

Ankara, , Turkey (Türkiye)

Research Site

Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

Research Site

Hanoi, , Vietnam

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Hà Nội, , Vietnam

Research Site

Ho Chi Minh City, , Vietnam

Research Site

Ho Chi Minh City, , Vietnam

Countries

United States; Argentina; Brazil; China; Hungary; India; Japan; Malaysia; Mexico; Peru; Russia; South Korea; Spain; Taiwan; Thailand; Turkey (Türkiye); Vietnam

References

Murat-Onana ML, Ramalingam SS, Janne PA, Gray JE, Ahn MJ, John T, Yatabe Y, Huang X, Rukazenkov Y, Javey M, Brown H, Li-Sucholeiki X. EGFR mutation testing across the osimertinib clinical program. Lung Cancer. 2025 Jun;204:108549. doi: 10.1016/j.lungcan.2025.108549. Epub 2025 Apr 18.

Reference Type: DERIVED

PMID: 40311309 (View on PubMed)

Lu S, Kato T, Dong X, Ahn MJ, Quang LV, Soparattanapaisarn N, Inoue T, Wang CL, Huang M, Yang JC, Cobo M, Ozguroglu M, Casarini I, Khiem DV, Sriuranpong V, Cronemberger E, Takahashi T, Runglodvatana Y, Chen M, Huang X, Grainger E, Ghiorghiu D, van der Gronde T, Ramalingam SS; LAURA Trial Investigators. Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC. N Engl J Med. 2024 Aug 15;391(7):585-597. doi: 10.1056/NEJMoa2402614. Epub 2024 Jun 2.

Reference Type: DERIVED

PMID: 38828946 (View on PubMed)

Tu CY, Hsia TC, Lin YC, Liang JA, Li CC, Chien CR. Efficacy of Definitive Radiotherapy for Patients with Clinical Stage IIIB or IIIC Lung Adenocarcinoma and Epidermal Growth Factor Receptor (EGFR) Mutations Treated Using First- or Second-Generation EGFR Tyrosine Kinase Inhibitors. Can Respir J. 2024 Mar 5;2024:8889536. doi: 10.1155/2024/8889536. eCollection 2024.

Reference Type: DERIVED

PMID: 38476120 (View on PubMed)

Lu S, Casarini I, Kato T, Cobo M, Ozguroglu M, Hodge R, van der Gronde T, Saggese M, Ramalingam SS. Osimertinib Maintenance After Definitive Chemoradiation in Patients With Unresectable EGFR Mutation Positive Stage III Non-small-cell Lung Cancer: LAURA Trial in Progress. Clin Lung Cancer. 2021 Jul;22(4):371-375. doi: 10.1016/j.cllc.2020.11.004. Epub 2021 Jan 6.

Reference Type: DERIVED

PMID: 33558193 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

2022-500860-36-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-001061-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D5160C00048

Identifier Type: -

Identifier Source: org_study_id