NCT04035486: FLAURA2

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)

Active, enrolled Phase 3 Results posted Last updated 10 October 2025

What this trial tests

Phase 3 trial testing Osimertinib in Non-Small Cell Lung Cancer in 587 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

2 July 2019

Primary endpoint
3 April 2023

22 December 2026

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	587
Start date	2 July 2019
Primary completion	3 April 2023
Estimated completion	22 December 2026
Sites	153 locations across Japan, Taiwan, Vietnam, South Korea, Philippines, Russia, Thailand, Czechia

Drugs / interventions tested

• Osimertinib (osimertinib) — full drug profile →
• Pemetrexed/Carboplatin
• Pemetrexed/Cisplatin

Conditions studied

• Non-Small Cell Lung Cancer — all drugs for Non-Small Cell Lung Cancer →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 110, any sex, with Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Adverse Events Graded by Common Terminology Criteria for Adverse Event v5 (Safety Run-In Treatment Arms Only) Primary · From first dose date to 28 days following last dose, up to 45 months

Adverse events were summarized by maximum reported Common Terminology Criteria for Adverse Event (CTCAE) grade, version 5.0. Grade 1 (Mild): asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living. Grade 3 (Severe or medically significant but not immediately life-threatening): hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 (Life-

Group	Value	95% CI
Safety Run-In: AZD9291 + Carboplatin + Pemetrexed	1
Safety Run-In: AZD9291 + Cisplatin + Pemetrexed	0
Safety Run-In: AZD9291 + Carboplatin + Pemetrexed	9
Safety Run-In: AZD9291 + Cisplatin + Pemetrexed	4
Safety Run-In: AZD9291 + Carboplatin + Pemetrexed	3
Safety Run-In: AZD9291 + Cisplatin + Pemetrexed	8
Safety Run-In: AZD9291 + Carboplatin + Pemetrexed	0
Safety Run-In: AZD9291 + Cisplatin + Pemetrexed	2

Progression-free Survival (PFS) (Randomized Component) Primary · Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.3 months)

Progression-free survival (PFS) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of asse

Group	Value	95% CI
Randomized: AZD9291 + Chemo	25.5	24.7 – NA
Randomized: AZD9291	16.7	14.1 – 21.3

Sensitivity Analysis for Progression-free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment (Randomized Component) Primary · Up to approximately 33 months after the first patient is randomized (maximum follow up of 33.2 months).

Sensitivity analysis for progression-free survival (PFS) by blinded independent central review (BICR) using Investigator assessment as defined by RECIST 1.1. Median progression free survival (months) calculated using the Kaplan-Meier method. Progression-free survival (PFS) is defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the ti

Group	Value	95% CI
Randomized: AZD9291 + Chemo	29.4	25.1 – NA
Randomized: AZD9291	19.9	16.6 – 25.3

Overall Survival (OS) (Safety Run-In Treatment Arms Only) Secondary · Up to 45 months (maximum follow up 44.6 months)

Overall survival is defined as the time from the date of first dose until death due to any causes. Subjects not known to have died at the time of analysis are censored at the last recorded date on which the subject was known to be alive. Median overall survival calculated using the Kaplan-Meier method. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.

Group	Value	95% CI
Overall Safety Run-In Participants	NA	34.0 – NA

Duration of Response (DoR) (Safety Run-In Treatment Arms Only) Secondary · Up to 45 months

Duration of response (DoR) is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression (i.e. date of progression free survival event or censoring - date of first response + 1). The end of response should coincide with the date of progression or death from any cause used for the progression free survival endpoint. The time of the initial response is defined as the latest of the dates contributing towards the first visit that was Complete response or Partial response that w

Group	Value	95% CI
Overall Safety Run-In Participants	27.5	± 13.48

Objective Response Rate (ORR) (Safety Run-In Treatment Arms Only) Secondary · Up to 45 months

Confirmed objective response rate (per RECIST 1.1 using Investigator assessments) is defined as the number (%) of subjects with at least 1 visit response of Completed Response (CR) or Partial Response (PR), where each CR or PR must be subsequently confirmed at least 4 weeks after the visit when the response was first observed with no evidence of progression between the initial and CR/PR confirmation visit. Confidence Interval is calculated using the exact Clopper-Pearson method. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received

Group	Value	95% CI
Overall Safety Run-In Participants	86.7	69.28 – 96.24

Depth of Response (Percent Change From Baseline in Tumor Diameter) (Safety Run-In Treatment Arms Only) Secondary · Up to 45 months

Depth of Response (percent change from Baseline in tumor diameter) is defined as the relative percent change in the sum of the longest diameters of RECIST 1.1 target lesions (TL) at the nadir in the absence of new lesions or progression of non-target lesions (NTL) compared to baseline. The best percentage change in TL size is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. Tumor assessments of the chest and abdomen (including the entire liver and both adrenal glands) were performed using RECIST 1.1 by the investigator on images from CT (

Group	Value	95% CI
Overall Safety Run-In Participants	-57.72	± 22.090

Disease Control Rate (DCR) by Investigator (Safety Run-In Treatment Arms Only) Secondary · Up to 45 months

Disease control rate is defined as the percentage of subjects who have a best overall response of Complete response (CR) or Partial response (PR) or Stable disease (SD) by RECIST 1.1 as assessed by the Investigator. For participants with a best overall response of SD, a RECIST assessment of SD must have been observed at least 6 weeks minus 1 week (at least 35 study days) following the first dose. Per the protocol, the safety run-in treatment arms were combined and analyzed regardless of chemotherapy received for consistency with the randomized component.

Complete Response (CR)

Group	Value	95% CI
Overall Safety Run-In Participants	3

Partial Response (PR)

Group	Value	95% CI
Overall Safety Run-In Participants	23

Stable Disease (SD)

Group	Value	95% CI
Overall Safety Run-In Participants	4

Overall Survival (OS) (Randomized Component) Secondary · Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)

Overall survival is defined as the time from the date of randomization until death due to any cause. Subjects not known to have died at the time of analysis are censored at the last recorded date on which the subject was known to be alive. Median overall Survival calculated using the Kaplan-Meier method.

Group	Value	95% CI
Randomized: AZD9291 + Chemo	NA	31.9 – NA
Randomized: AZD9291	NA	NA – NA

Landmark Overall Survival (LOS) at 1, 2, and 3 Years (Randomized Component) Secondary · Up to approximately 33 months after the first patient is randomized (maximum follow up of 34.1 months)

Landmark Overall Survival at 1, 2, and 3 years looks at the percent of patients alive at 1, 2 and 3 year time points. Overall survival at 36 months not included to data cut off prior to 36-month timepoint. Overall survival percentage calculated using the Kaplan-Meier method.

Overall survival at 12 months (%)

Group	Value	95% CI
Randomized: AZD9291 + Chemo	88.8	84.4 – 92.0
Randomized: AZD9291	92.0	88.1 – 94.7

Overall survival at 24 months (%)

Group	Value	95% CI
Randomized: AZD9291 + Chemo	78.9	73.4 – 83.4
Randomized: AZD9291	73.0	66.9 – 78.1

Objective Response Rate (ORR) (Randomized Component) Secondary · Up to approximately 33 months after the first patient is randomized.

Objective Response Rate (ORR) (per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments) is defined as the number (%) of patients with at least 1 visit response of Complete Response or Partial Response. Data obtained up until progression, or the last evaluable assessment in the absence of progression, was included in the assessment of Objective Response Rate. The investigator-assessed ORR was summarized with a logistic regression stratified by race (Chinese/Asian vs. Non-Chinese/Asian vs. Non-Asian), WHO performance status (0 vs. 1), and method

Group	Value	95% CI
Randomized: AZD9291 + Chemo	84.40	79.51 – 88.30
Randomized: AZD9291	77.10	71.52 – 81.85

Duration of Response (DoR) (Randomized Component) Secondary · Up to approximately 33 months after the first patient is randomized.

The duration of response is defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response should coincide with the date of progression or death from any cause used for the progression-free survival endpoint. The time of the initial response is defined as the latest of the dates contributing towards the first response of Partial response or Complete response. Median values of the duration of response, along with two-sided 95% CI in each treatment group were computed using the Kaplan-Meier

Group	Value	95% CI
Randomized: AZD9291 + Chemo	24.0	20.9 – 27.8
Randomized: AZD9291	15.3	12.7 – 19.4

Adverse events — posted to ClinicalTrials.gov

Time frame: Includes treatment emergent adverse events with onset date on or after the date of first dose and up to and including 28 days following discontinuation of treatment but prior to the start of a new anti-cancer therapy. For the Safety Run-In treatment arms, this was up to 45 months, or the data cut-off. For the Randomized treatment arms, this was up to 33 months, or the data cut-off.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Safety Run-In: AZD9291 + Carboplatin + Pemetrexed

Serious: 5/15 (33%)

Deaths: 6/15

Safety Run-In: AZD9291 + Cisplatin + Pemetrexed

Serious: 6/15 (40%)

Deaths: 3/15

Randomized: AZD9291 + Chemo

Serious: 104/276 (38%)

Deaths: 71/279

Randomized: AZD9291

Serious: 53/275 (19%)

Deaths: 78/278

Serious adverse events (147 terms)

Reaction	System	Safety Run-In: AZD9291 + C…	Safety Run-In: AZD9291 + C…	Randomized: AZD9291 + Chemo	Randomized: AZD9291
Anaemia	Blood and lymphatic system disorders	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—
COVID-19 pneumonia	Infections and infestations	—	—	—	—
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—
Cardiac failure	Cardiac disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Drug-induced liver injury	Hepatobiliary disorders	—	—	—	—
Coronary artery stenosis	Cardiac disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—
Nephrolithiasis	Renal and urinary disorders	—	—	—	—
Renal failure	Renal and urinary disorders	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Other adverse events (164 terms — click to expand)

Reaction	System	Safety Run-In: AZD9291 + C…	Safety Run-In: AZD9291 + C…	Randomized: AZD9291 + Chemo	Randomized: AZD9291
Anaemia	Blood and lymphatic system disorders	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Paronychia	Infections and infestations	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—
Neutrophil count decreased	Investigations	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—
COVID-19	Infections and infestations	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—
White blood cell count decreased	Investigations	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—
Dermatitis acneiform	Skin and subcutaneous tissue disorders	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—
Leukopenia	Blood and lymphatic system disorders	—	—	—	—
Weight decreased	Investigations	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Asthenia	General disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Mucosal inflammation	General disorders	—	—	—	—
Electrocardiogram QT prolonged	Investigations	—	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—	—	—

Most-reported serious reactions: Anaemia, COVID-19, Pneumonia, Febrile neutropenia, Platelet count decreased, Pulmonary embolism, COVID-19 pneumonia, Interstitial lung disease.

Data from ClinicalTrials.gov NCT04035486 adverse events section.

Sponsor's own description

The reason for the study is to find out if an experimental combination of an oral medication called osimertinib (TAGRISSO®) when used in combination with chemotherapy is more effective than giving osimertinib alone for the treatment of locally advanced or metastatic non-small cell lung cancer. Some lung cancers are due to mutations in the Deoxyribonucleic acid (DNA) which, if known, can help physicians decide the best treatment for their patients. One type of mutation can occur in the gene that produces a protein on the surface of cells called the Epidermal Growth Factor Receptor (EGFR).

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Osimertinib with or without Chemotherapy in <i>EGFR</i>-Mutated Advanced NSCLC.
   Planchard D, Jänne PA, Cheng Y, Yang JC, et al · · 2023 · cited 471× · PMID 37937763 · DOI 10.1056/nejmoa2306434
2. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management.
   Cooper AJ, Sequist LV, Lin JJ. · · 2022 · cited 382× · PMID 35534623 · DOI 10.1038/s41571-022-00639-9
3. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.
   Fu K, Xie F, Wang F, Fu L. · · 2022 · cited 271× · PMID 36482474 · DOI 10.1186/s13045-022-01391-4
4. Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer (Review).
   He J, Huang Z, Han L, Gong Y, et al · · 2021 · cited 232× · PMID 34558640 · DOI 10.3892/ijo.2021.5270
5. Oncogenic driver mutations in non-small cell lung cancer: Past, present and future.
   Chevallier M, Borgeaud M, Addeo A, Friedlaender A. · · 2021 · cited 198× · PMID 33959476 · DOI 10.5306/wjco.v12.i4.217
6. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for <i>EGFR</i>-mutated resectable non-small-cell lung cancer: NeoADAURA.
   Tsuboi M, Weder W, Escriu C, Blakely C, et al · · 2021 · cited 150× · PMID 34278827 · DOI 10.2217/fon-2021-0549
7. Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC.
   Nagasaka M, Zhu VW, Lim SM, Greco M, et al · · 2021 · cited 144× · PMID 33338652 · DOI 10.1016/j.jtho.2020.11.028
8. Emerging strategies to overcome resistance to third-generation EGFR inhibitors.
   Shi K, Wang G, Pei J, Zhang J, et al · · 2022 · cited 112× · PMID 35840984 · DOI 10.1186/s13045-022-01311-6