NCT01802632: AURA

AZD9291 First Time In Patients Ascending Dose Study

Completed Phase 1, PHASE2 Results posted Last updated 18 January 2024

What this trial tests

Phase 1, PHASE2 trial testing AZD9291 in Advanced Non Small Cell Lung Cancer in 603 participants. Completed in 13 December 2023.

Timeline

4 March 2013

Primary endpoint
1 May 2015

13 December 2023

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	603
Start date	4 March 2013
Primary completion	1 May 2015
Estimated completion	13 December 2023
Sites	45 locations across France, Italy, Japan, Taiwan, United Kingdom, Germany, South Korea, Australia

Drugs / interventions tested

• AZD9291 — full drug profile →

Conditions studied

• Advanced Non Small Cell Lung Cancer — all drugs for Advanced Non Small Cell Lung Cancer →
• Advanced (Inoperable) Non Small Cell Lung Cancer — all drugs for Advanced (Inoperable) Non Small Cell Lung Cancer →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Advanced Non Small Cell Lung Cancer or Advanced (Inoperable) 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.

Objective Response Rate (ORR) for Dose Expansion Population Primary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by investigator assessment) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.

Group	Value	95% CI
Dose Expansion	61.7	54.1 – 68.9

Best Objective Response (BOR) for Dose Escalation Population Primary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 25 months (at time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) o

Partial Response

Group	Value	95% CI
Dose Escalation	58.1	54.1 – 68.9

Stable disease

Group	Value	95% CI
Dose Escalation	19.4

Progressive disease

Group	Value	95% CI
Dose Escalation	16.1

Not evaluable

Group	Value	95% CI
Dose Escalation	6.5

Duration of Response (DoR) for Dose Expansion Population Secondary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR was defined as the time from the date of first documented response (CR or PR that was subsequently confirmed) until the date of documented progression (PD) or death in the absence of disease progression (by investigator assessment).

Group	Value	95% CI
Dose Expansion	11.1	8.3 – 13.8

Progression-Free Survival (PFS) for Dose Expansion Population Secondary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 21 months (at time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of first dose until the date of PD (by independent central review) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from AZD9291 therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed

Group	Value	95% CI
Dose Expansion	9.7	8.3 – 12.5

Objective Response Rate (ORR) for Extension Population Primary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR (by independent central review) that was confirmed at least 4 weeks later, prior to progression or further anti-cancer therapy.

Group	Value	95% CI
80mg AZD9291 Extension	61.3	54.2 – 68.1

Best Objective Response (BOR) for 80mg AZD9291 Extension Population Secondary · RECIST tumour assessments every 6 weeks from randomisation until objective disease progression, up to approximately 12 months (at the time of analysis)

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) o

Complete Response

Group	Value	95% CI
80mg AZD9291 Extension	0.5	54.1 – 68.9

Partial response

Group	Value	95% CI
80mg AZD9291 Extension	70.1

Stable disease

Group	Value	95% CI
80mg AZD9291 Extension	22.9

Progressive disease

Group	Value	95% CI
80mg AZD9291 Extension	6.0

Not evaluable

Group	Value	95% CI
80mg AZD9291 Extension	0.5

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs from start of study drug until 28 days post study treatment discontinuation, up to approximately 25 months (at time of analysis).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD9291 80mg Extension

Serious: 41/201 (20%)

Deaths: —

Dose Escalation

Serious: 9/31 (29%)

Deaths: —

Dose Expansion

Serious: 78/271 (29%)

Deaths: —

First Line

Serious: 14/60 (23%)

Deaths: —

80mg Tablet

Serious: 4/12 (33%)

Deaths: —

Japan Cytology

Serious: 4/28 (14%)

Deaths: —

Serious adverse events (130 terms)

Reaction	System	AZD9291 80mg Extension	Dose Escalation	Dose Expansion	First Line	80mg Tablet	Japan Cytology
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Influenza	Infections and infestations	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Cerebrovascular accident	Nervous system disorders	—	—	—	—	—	—
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—	—	—	—
Lung infection	Infections and infestations	—	—	—	—	—	—
Subdural haematoma	Injury, poisoning and procedural complications	—	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—	—	—
Ischaemic stroke	Nervous system disorders	—	—	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Disseminated intravascular coagulation	Blood and lymphatic system disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—

Other adverse events (97 terms — click to expand)

Reaction	System	AZD9291 80mg Extension	Dose Escalation	Dose Expansion	First Line	80mg Tablet	Japan Cytology
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—
Paronychia	Infections and infestations	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—
Dermatitis acneiform	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—
Skin fissures	Skin and subcutaneous tissue disorders	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—
Platelet count decreased	Investigations	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—	—	—	—
Dry eye	Eye disorders	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—

Most-reported serious reactions: Pulmonary embolism, Pneumonia, Diarrhoea, Dyspnoea, Nausea, Pleural effusion, Pneumonitis, Anaemia.

Data from ClinicalTrials.gov NCT01802632 adverse events section.

Sponsor's own description

This study will treat patients with advanced NSCLC who have already received at least one course of specific anti-cancer treatment but the tumour has started to re-grow following that treatment. This is the first time this drug has ever been tested in patients, and so it will help to understand what type of side effects may occur with the drug treatment, it will measure the levels of drug in the body, it will also measure the anti-cancer activity. By using these pieces of information together the best dose of this drug to use in further clinical trials will be selected.

Publications & conference data

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

1. AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer.
   Cross DA, Ashton SE, Ghiorghiu S, Eberlein C, et al · · 2014 · cited 1752× · PMID 24893891 · DOI 10.1158/2159-8290.cd-14-0337
2. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer.
   Jänne PA, Yang JC, Kim DW, Planchard D, et al · · 2015 · cited 1624× · PMID 25923549 · DOI 10.1056/nejmoa1411817
3. Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M.
   Thress KS, Paweletz CP, Felip E, Cho BC, et al · · 2015 · cited 1237× · PMID 25939061 · DOI 10.1038/nm.3854
4. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer.
   Oxnard GR, Thress KS, Alden RS, Lawrance R, et al · · 2016 · cited 645× · PMID 27354477 · DOI 10.1200/jco.2016.66.7162
5. Current Challenges and Opportunities in Treating Glioblastoma.
   Shergalis A, Bankhead A, Luesakul U, Muangsin N, et al · · 2018 · cited 612× · PMID 29669750 · DOI 10.1124/pr.117.014944
6. Management of acquired resistance to EGFR TKI-targeted therapy in advanced non-small cell lung cancer.
   Wu SG, Shih JY. · · 2018 · cited 577× · PMID 29455650 · DOI 10.1186/s12943-018-0777-1
7. Assessment of Resistance Mechanisms and Clinical Implications in Patients With EGFR T790M-Positive Lung Cancer and Acquired Resistance to Osimertinib.
   Oxnard GR, Hu Y, Mileham KF, Husain H, et al · · 2018 · cited 574× · PMID 30073261 · DOI 10.1001/jamaoncol.2018.2969
8. Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity.
   Ballard P, Yates JW, Yang Z, Kim DW, et al · · 2016 · cited 556× · PMID 27435396 · DOI 10.1158/1078-0432.ccr-16-0399