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

NCT03521154 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: D5160C000482022-500860-36-002018-001061-16
• Study Type: interventional
• Target: 216
• Locations: 17 countries
• Sites: 118

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

Conditions

Non Small Cell Lung Cancer (Stage III)

Keywords

Phase III; Osimertinib; Non Small Cell Lung Cancer (Stage III); Unresectable NSCLC; EGFR; chemoradiation therapy

Outcome Measures

Primary Outcomes (1)

• 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

  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 (15)

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

  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

  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)

  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)

  Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months

• Overall Survival (Duration)

  Date of randomisation to date of death by any cause. Assessed up to a maximum of approximately 63 months

Study Arms (2)

Osimertinib

EXPERIMENTAL

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

Drug: Osimertinib 80mg/40mg

Placebo Osimertinib

PLACEBO COMPARATOR

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

Drug: Placebo Osimertinib 80mg/40mg

Interventions

Osimertinib 80mg/40mg 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.

Osimertinib

Placebo Osimertinib 80mg/40mg 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

Placebo Osimertinib

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged at least 18 years.
• 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).
• 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).
• 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).
• Chemoradiation must be completed ≤6 weeks prior to randomization.
• Patients must not have had disease progression during or following definitive platinum-based, chemoradiation therapy.
• World Health Organization (WHO) performance status of 0 or 1.
• Life expectancy \>12 weeks at Day 1.
• 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.

You may not qualify if:

• Mixed small cell and non-small cell lung cancer histology
• History of interstitial lung disease (ILD) prior to chemoradiation
• Symptomatic pneumonitis following chemoradiation
• Any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) \> Grade 2 from the prior chemoradiation therapy
• 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
• Inadequate bone marrow reserve or organ function
• 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.
• 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).
• 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 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 treatment with EGFR-TKI therapy
• Major surgery as defined by the investigator within 4 weeks of the first dose of study drug.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (118)

Research Site

Duarte, California, 91010, United States

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Atlanta, Georgia, 30322, United States

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Florham Park, New Jersey, 07932, United States

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Salt Lake City, Utah, 84106, United States

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Madison, Wisconsin, 53792, United States

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Ciudad Autónoma de Bs. As., 1426, Argentina

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Ciudad Autónoma de Bs. As., C1199ABB, Argentina

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Mar del Plata, 7600, Argentina

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Rosario, 2000, Argentina

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San Salvador de Jujuy, 4600, Argentina

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Barretos, 14784-400, Brazil

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Curitiba, 81520-060, Brazil

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Florianópolis, 88034-000, Brazil

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Fortaleza, 60336-045, Brazil

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Porto Alegre, 90160-093, Brazil

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Porto Alegre, 90610-000, Brazil

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Ribeirão Preto, 14021-636, Brazil

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São Paulo, 01221-0100, Brazil

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São Paulo, 01246-000, Brazil

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Beijing, 100021, China

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Beijing, 100730, China

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Changchun, 130000, China

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Changsha, 410013, China

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Chengdu, 610041, China

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Guangzhou, 510100, China

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Hangzhou, 310003, China

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Hangzhou, 310006, China

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Hangzhou, 310022, China

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Jinan, 250117, China

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Linhai, 317000, China

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Shanghai, 200030, China

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Shanghai, 200032, China

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Ürümqi, 830099, China

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Wuhan, 430022, China

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Wuhan, 430030, China

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Budapest, 1083, Hungary

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Budapest, 1121, Hungary

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Gyöngyös - Mátraháza, 3200, Hungary

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Pécs, 7623, Hungary

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Bangalore, 560068, India

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Gurgaon, 122001, India

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Hubli, 580025, India

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Karamsad, 388325, India

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Kolkata, 700160, India

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Nashik, 422002, India

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New Delhi, 110063, India

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New Delhi, 110085, India

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New Delhi, 11029, India

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Hiroshima, 734-8551, Japan

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Kanazawa, 920-8641, Japan

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Kashiwa, 227-8577, Japan

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Nagoya, 460-0001, Japan

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Niigata, 951-8566, Japan

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Osaka, 541-8567, Japan

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Sakaishi, 591-8555, Japan

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Sapporo, 003-0804, Japan

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Sayama, 589-8511, Japan

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Sendai, 981-0914, Japan

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Shinjuku-ku, 160-0023, Japan

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Sunto-gun, 411-8777, Japan

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Yokohama, 241-8515, Japan

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George Town, 10450, Malaysia

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Kuala Lumpur, 59100, Malaysia

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Kuala Selangor, 46050, Malaysia

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Mérida, 97134, Mexico

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Lima, LIMA 31, Peru

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Lima, Lima 32, Peru

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Lima, LIMA 34, Peru

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Lima, LIMA 41, Peru

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San Isidro, 27, Peru

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Kazan', 420029, Russia

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Kostroma, 156005, Russia

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Moscow, 121205, Russia

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Novisibirsk, 630082, Russia

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Obninsk, 249036, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197758, Russia

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Ufa, 450054, Russia

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Cheongju-si, 28644, South Korea

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Incheon, 21565, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Barcelona, 08003, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Málaga, 29010, Spain

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San Sebastián, 20014, Spain

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Seville, 41009, Spain

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Valencia, 46009, Spain

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Kaohsiung City, 83301, Taiwan

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Taichung, 402, Taiwan

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Taichung, 40447, Taiwan

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Taichung, 40705, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 10002, Taiwan

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Taipei, 11217, Taiwan

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Taoyuan, 00333, Taiwan

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Bangkok, 10300, Thailand

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Bangkok, 10330, Thailand

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Bangkok, 10400, Thailand

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Bangkok, 10700, Thailand

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Hat Yai, 90110, Thailand

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Khon Kaen, 40002, Thailand

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Lampang, 52000, Thailand

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Mueang, 50200, Thailand

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Adana, 01120, Turkey (Türkiye)

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Adapazarı, 54290, Turkey (Türkiye)

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Ankara, 06280, Turkey (Türkiye)

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Ankara, 6200, Turkey (Türkiye)

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Ankara, Turkey (Türkiye)

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Istanbul, 34030, Turkey (Türkiye)

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Istanbul, 34854, Turkey (Türkiye)

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Izmir, 35620, Turkey (Türkiye)

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Hanoi, 100000, Vietnam

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Hà Nội, 100000, Vietnam

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Ho Chi Minh City, 700000, Vietnam

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Ho Chi Minh City, 70000, Vietnam

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Related Publications (6)

• 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, Sriuranpong V, Cronemberger E, Takahashi T, Runglodvatana Y, Chen M, Huang X, Grainger E, Ghiorghiu D, van der Gronde T, Ramalingam SS. A plain language review of results from the LAURA study: osimertinib after chemoradiotherapy for patients with EGFR-mutated non-small cell lung cancer that cannot be removed by surgery. Future Oncol. 2026 May;22(11):1247-1262. doi: 10.1080/14796694.2026.2652543. Epub 2026 Apr 27.

  PMID: 42037107 DERIVED

• Arriola E, Casarini I, Ozguroglu M, Huang M, Takahashi T, Lai X, Goto K, Maneenil K, Lee KH, Cobo M, Valdiviezo N, Evans A, Bolanos A, Huang X, Lai R, Ramalingam SS. Patient-reported outcomes from the LAURA study: osimertinib in patients with unresectable stage III EGFR-mutated non-small cell lung cancer after definitive chemoradiotherapy. Eur J Cancer. 2026 Apr 12;240:116744. doi: 10.1016/j.ejca.2026.116744. Online ahead of print.

  PMID: 42019226 DERIVED

• 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.

  PMID: 40311309 DERIVED

• 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.

  PMID: 38828946 DERIVED

• 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.

  PMID: 38476120 DERIVED

• 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.

  PMID: 33558193 DERIVED

Related Links

• D5160C00048\_CSP\_redacted
• D5160C00048\_SAP\_redacted
• D5160C00048\_CSR synopsis\_redacted

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

As per CSP Section 7.2, patient monitoring during treatment with open-label osimertinib is monitored by the investigator per local clinical guidance. Serious AEs and AESIs are reported in the eCRF but were not analyzed/tabulated at the time of primary analysis. Safety assessments are to be performed as per local clinical practice and not collected as part of study data capture in line with the protocol.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca Clinical Study Information Center

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Suresh S Ramalingam, MD

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

  PRINCIPAL INVESTIGATOR

• Shun Lu, MD

  Shanghai Chest Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2018
• First Posted: May 11, 2018
• Study Start: July 19, 2018
• Primary Completion: January 5, 2024
• Study Completion (Estimated): October 29, 2027
• Last Updated: May 5, 2026
• Results First Posted: April 3, 2025

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

RU (8); TU (8); TW (8); CN (16); TH (8); MY (3); PE (5); ME (1); IN (9); VN (4); AR (5); HU (4); US (5); BR (9); ES (7); JP (13); KR (5)