A Study of Osimertinib With or Without Chemotherapy as 1st Line Treatment in Patients With Mutated Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer (FLAURA2)
NCT ID: NCT04035486
Last Updated: 2025-10-10
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE3
587 participants
INTERVENTIONAL
2019-07-02
2026-12-22
Brief Summary
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Osimertinib is an Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) that targets Epidermal Growth Factor Receptor (EGFR) mutations. Unfortunately, despite the benefit observed for patients treated with osimertinib, the vast majority of cancers are expected to develop resistance to the drug over time. The exact reasons why resistance develops are not fully understood but based upon clinical research it is hoped that combining osimertinib with another type of anti-cancer therapy known as chemotherapy will delay the onset of resistance and the worsening of a patient's cancer.
In total the study aims to enroll approximately 586 patients, consisting of approximately 30 patients who will participate in a safety run-in component of the trial, and approximately 556 who will receive osimertinib alone or osimertinib in combination with chemotherapy in the main trial. In the main part of the trial there is a one in two chance of receiving osimertinib alone, and the treatment is decided at random by a computer.
The study involves a Screening Period, Treatment Period, and Follow up Period. Whilst receiving study medication, it is expected patients will attend, on average, approximately 15 visits over the first 12 months and then approximately 4 visits per year afterwards. Each visit will last about 2 to 6 hours depending on the arrangement of medical assessments by the study centre.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Osimertinib 80mg QD
Osimertinib (AZD9291) 80mg QD.
All patients randomized into this will only receive Osimertinib 80mg.
Dose may be reduced to allow for the management of IP related toxicity.
Osimertinib
Drug: Osimertinib (Oral)
Other Names:
AZD9291
Osimertinib 80 mg QD and platinum-based chemotherapy
Osimertinib 80 mg in combination with pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Dose may be reduced to allow for the management of IP related toxicity.
Pemetrexed/Carboplatin
Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Pemetrexed/Cisplatin
Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Interventions
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Osimertinib
Drug: Osimertinib (Oral)
Other Names:
AZD9291
Pemetrexed/Carboplatin
Drug: Pemetrexed (500 mg/m2) plus carboplatin (AUC5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Pemetrexed/Cisplatin
Drug: Pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by Osimertinib daily with pemetrexed maintenance (500 mg/m2) every 3 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC). NSCLC of mixed histology is allowed.
3. Newly diagnosed locally advanced (clinical stage IIIB, IIIC) or metastatic Non-Small Cell Lung Cancer (NSCLC) (clinical stage IVA or IVB) or recurrent Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
4. The tumor harbors 1 of the 2 common epidermal growth factor receptor (EGFR) mutations known to be associated with Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) sensitivity (Ex19del or L858R), either alone or in combination with other epidermal growth factor receptor (EGFR) mutations, which may include T790M.
5. Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy.
6. WHO PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks.
7. Life expectancy \>12 weeks at Day 1.
8. Willing to use contraception as appropriate during the study and for a period of time after discontinuing study treatment.
Exclusion Criteria
2. Past medical history of Interstitial Lung Disease (ILD), drug-induced Interstitial Lung Disease, radiation pneumonitis that required steroid treatment, or any evidence of clinically active Interstitial Lung Disease.
3. 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 jeopardize compliance with the protocol, or active infection including Hep. B, Hep. C and HIV. Screening for chronic conditions is not required. Active infection will include any patients receiving treatment for infection.
4. QT prolongation or any clinically important abnormalities in rhythm.
5. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
* Absolute neutrophil count below the lower limit of normal (\<LLN)
* Platelet count below the LLN
* Hemoglobin \<90 g/L. The use of granulocyte colony stimulating factor support, platelet transfusion and blood transfusions to meet these criteria is not permitted.
* ALT \>2.5 x the upper limit of normal (ULN) if no demonstrable liver metastases or \>5 x ULN in the presence of liver metastases
* AST \>2.5 x ULN if no demonstrable liver metastases or \>5 x ULN in the presence of liver metastases
* Total bilirubin \>1.5 x ULN if no liver metastases or \>3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases
* Creatinine clearance \<60 mL/min calculated by Cockcroft and Gault equation or 24 hour urine collection (refer to Appendix I for appropriate calculation)
6. 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.
7. Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiation including chemotherapy, biologic therapy, immunotherapy, or any investigational drug. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapies, investigational agents are permitted as long as treatment was completed at least 12 months prior to the development of recurrent disease.
8. Prior treatment with an Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).
9. Major surgery within 4 weeks of the first dose of investigational product (IP). Procedures such as placement of vascular access, biopsy via mediastinoscopy or biopsy via video assisted thoracoscopic surgery are permitted.
10. Radiotherapy treatment to more than 30% of the bone marrow or( with a wide field of radiation within 4 weeks of the first dose of investigational product (IP).
11. History of hypersensitivity to active or inactive excipients of investigational product (IP) or drugs with a similar chemical structure or class to investigational product (IP).
18 Years
110 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Responsible Party
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Principal Investigators
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Pasi A. Jänne, MD
Role: PRINCIPAL_INVESTIGATOR
Dana Farber Cancer Institute, 450 Brookline Avenue, LC4114, Boston, MA 02215, USA
Kunihiko Kobayashi, MD
Role: PRINCIPAL_INVESTIGATOR
Department of Respiratory Medicine, Saitama Medical University International Medical Center, Saitama, Japan
David Planchard, MD
Role: PRINCIPAL_INVESTIGATOR
Department of Medical Oncology - Institut Gustave Roussy (IGR) - Villejuif - France
Locations
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Research Site
Bellflower, California, United States
Research Site
Fullerton, California, United States
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La Jolla, California, United States
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Santa Monica, California, United States
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Santa Rosa, California, United States
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West Hollywood, California, United States
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Whittier, California, United States
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Orlando, Florida, United States
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Tampa, Florida, United States
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Kansas City, Kansas, United States
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Louisville, Kentucky, United States
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Boston, Massachusetts, United States
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Henderson, Nevada, United States
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Albany, New York, United States
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Canton, Ohio, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Blacksburg, Virginia, United States
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Fairfax, Virginia, United States
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Vancouver, Washington, United States
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Buenos Aires, , Argentina
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Buenos Aires, , Argentina
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CABA, , Argentina
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CABA, , Argentina
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Ciudad de Buenos Aires, , Argentina
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Córdoba, , Argentina
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Santa Fe, , Argentina
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Camperdown, , Australia
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Chermside, , Australia
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Elizabeth Vale, , Australia
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Heidelberg, , Australia
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Kogarah, , Australia
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Melbourne, , Australia
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Barretos, , Brazil
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Florianópolis, , Brazil
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Londrina, , Brazil
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Porto Alegre, , Brazil
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Ribeirão Preto, , Brazil
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São José do Rio Preto, , Brazil
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São Paulo, , Brazil
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São Paulo, , Brazil
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Vitória, , Brazil
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Calgary, Alberta, Canada
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Edmonton, Alberta, Canada
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Toronto, Ontario, Canada
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Santiago, , Chile
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Santiago, , Chile
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Temuco, , Chile
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Viña del Mar, , Chile
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Beijing, , China
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Beijing, , China
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Beijing, , China
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Changchun, , China
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Changsha, , China
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Chengdu, , China
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Chongqing, , China
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Guangzhou, , China
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Haikou, , China
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Hangzhou, , China
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Hangzhou, , China
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Harbin, , China
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Hefei, , China
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Jinan, , China
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Nanjing, , China
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Shanghai, , China
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Shanghai, , China
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Shenyang, , China
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Ürümqi, , China
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Wuhan, , China
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Xi'an, , China
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Zhengzhou, , China
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Olomouc, , Czechia
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Ostrava - Vitkovice, , Czechia
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Prague, , Czechia
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Prague, , Czechia
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Bordeaux, , France
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Lyon, , France
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Montpellier, , France
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Villejuif, , France
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Belagavi, , India
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Bengaluru, , India
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Gurgaon, , India
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Kolkata, , India
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New Delhi, , India
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Pune, , India
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Bunkyō City, , Japan
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Bunkyō City, , Japan
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Fukuoka, , Japan
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Hidaka-shi, , Japan
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Himeji-shi, , Japan
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Iwakuni-shi, , Japan
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Kanazawa, , Japan
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Kashiwa, , Japan
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Kōtoku, , Japan
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Osaka, , Japan
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Sakaishi, , Japan
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Sapporo, , Japan
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Sendai, , Japan
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Sunto-gun, , Japan
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Yokohama, , Japan
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Arequipa, , Peru
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Lima, , Peru
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Lima, , Peru
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Lima, , Peru
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San Isidro, , Peru
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Cebu City, , Philippines
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Davao City, , Philippines
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Iloilo City, , Philippines
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Las Piñas, , Philippines
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Legaspi, , Philippines
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Quezon City, , Philippines
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Quezon City, , Philippines
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Moscow, , Russia
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Moscow, , Russia
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Murmansk, , Russia
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Saint Petersburg, , Russia
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Saint Petersburg, , Russia
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Saint Petersburg, , Russia
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Syktyvkar, , Russia
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Bratislava, , Slovakia
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Košice, , Slovakia
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Poprad, , Slovakia
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Johannesburg, , South Africa
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Port Elizabeth, , South Africa
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Rondebosch, , South Africa
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Cheongju-si, , South Korea
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Goyang-si, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Changhua, , Taiwan
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Hualien City, , Taiwan
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Kaohsiung City, , Taiwan
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Taichung, , Taiwan
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Taichung, , Taiwan
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Taipei, , Taiwan
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Taipei, , Taiwan
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Bangkok, , Thailand
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Bangkok, , Thailand
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Bangkok, , Thailand
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Hat Yai, , Thailand
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Khon Kaen, , Thailand
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Muang, , Thailand
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Cambridge, , United Kingdom
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Leicester, , United Kingdom
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Liverpool, , United Kingdom
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Maidstone, , United Kingdom
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Manchester, , United Kingdom
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Hanoi, , Vietnam
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Ho Chi Minh City, , Vietnam
Countries
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References
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Janne PA, Planchard D, Kobayashi K, Yang JC, Liu Y, Valdiviezo N, Kim TM, Jiang L, Kagamu H, Yanagitani N, Wang J, Biswas B, Poltoratskiy A, Neron Y, Rojas C, Koubkova L, Escriu C, Ezeife DA, Mann H, Armenteros-Monterroso E, Rukazenkov Y, Lee CK; FLAURA2 Investigators. Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2025 Oct 17. doi: 10.1056/NEJMoa2510308. Online ahead of print.
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.
Janne PA, Planchard D, Kobayashi K, Cheng Y, Lee CK, Valdiviezo N, Laktionov K, Yang TY, Yu Y, Kato T, Jiang L, Chewaskulyong B, Lucien Geater S, Maurel JM, Rojas C, Takahashi T, Havel L, Shepherd FA, Tanaka K, Ghiorghiu D, Amin NP, Armenteros-Monterroso E, Huang X, Chaudhry AA, Yang JC. CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2024 Mar 1;42(7):808-820. doi: 10.1200/JCO.23.02219. Epub 2023 Dec 2.
Planchard D, Janne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. doi: 10.1056/NEJMoa2306434. Epub 2023 Nov 8.
Planchard D, Feng PH, Karaseva N, Kim SW, Kim TM, Lee CK, Poltoratskiy A, Yanagitani N, Marshall R, Huang X, Howarth P, Janne PA, Kobayashi K. Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small-cell lung cancer: safety run-in results from the FLAURA2 study. ESMO Open. 2021 Oct;6(5):100271. doi: 10.1016/j.esmoop.2021.100271. Epub 2021 Sep 17.
White MN, Piotrowska Z, Stirling K, Liu SV, Banwait MK, Cunanan K, Sequist LV, Wakelee HA, Hausrath D, Neal JW. Combining Osimertinib With Chemotherapy in EGFR-Mutant NSCLC at Progression. Clin Lung Cancer. 2021 May;22(3):201-209. doi: 10.1016/j.cllc.2021.01.010. Epub 2021 Jan 27.
Asahina H, Tanaka K, Morita S, Maemondo M, Seike M, Okamoto I, Oizumi S, Kagamu H, Takahashi K, Kikuchi T, Isobe T, Sugio K, Kobayashi K. A Phase II Study of Osimertinib Combined With Platinum Plus Pemetrexed in Patients With EGFR-Mutated Advanced Non-Small-cell Lung Cancer: The OPAL Study (NEJ032C/LOGIK1801). Clin Lung Cancer. 2021 Mar;22(2):147-151. doi: 10.1016/j.cllc.2020.09.023. Epub 2020 Oct 16.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Other Identifiers
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2019-000650-61
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D5169C00001
Identifier Type: -
Identifier Source: org_study_id
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