Trial Outcomes & Findings for Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (NCT NCT02094261)

NCT ID: NCT02094261

Last Updated: 2024-11-06

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

210 participants

Primary outcome timeframe

RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Results posted on

2024-11-06

Participant Flow

First patient enrolled: 28 April 2014, Data cut off: 1 May 2015. The study was open for enrolment at 44 study centres in Canada (3), Hong Kong (2), Italy (5), Japan (14), South Korea (3), Spain (6), Taiwan (2), and the USA (9). Recruitment has closed and primary analyses have been performed but study is still on-going.

472 patients were enrolled (signed informed consent). Patients were assigned to treatment if they met all the inclusion and none of the exclusion criteria. 262 patients were enrolled but failed inclusion/exclusion criteria and so were not eligible to be assigned treatment. The remaining 210 patients received treatment.

Participant milestones

Participant milestones
Measure	AZD9291 80mg Daily single dose of AZD9291 80mg
Overall Study STARTED	210
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	210

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD9291 80mg Daily single dose of AZD9291 80mg
Overall Study Death	24
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	4
Overall Study Ongoing Study at Data Cut-off	181

Baseline Characteristics

Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD9291 80mg n=210 Participants Daily single dose of AZD9291 80mg
Age, Continuous	62.9 Years STANDARD_DEVIATION 10.91 • n=5 Participants
Age, Customized <50 Years	20 Participants n=5 Participants
Age, Customized >=50-<65 Years	88 Participants n=5 Participants
Age, Customized >=65-<75 Years	69 Participants n=5 Participants
Age, Customized >=75 Years	33 Participants n=5 Participants
Sex: Female, Male Female	146 Participants n=5 Participants
Sex: Female, Male Male	64 Participants n=5 Participants
Race/Ethnicity, Customized Asian	132 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	3 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian Or Other Pacific Islander	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants
Race/Ethnicity, Customized White	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Population: All patients who received at least 1 dose of study treatment and had measurable disease at baseline according to the independent review of baseline imaging data.

Outcome measures

Outcome measures
Measure	AZD9291 80mg n=199 Participants Daily single dose of AZD9291 80mg
Objective Response Rate (ORR)	70.9 % of participants Interval 64.0 to 77.1

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Population: All patients who received at least 1 dose of study treatment, had measurable disease at baseline according to the independent review of baseline imaging data and had confirmed response.

Outcome measures

Outcome measures
Measure	AZD9291 80mg n=141 Participants Daily single dose of AZD9291 80mg
Duration of Response (DoR)	7.8 months Interval 1.3 to 8.4

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Population: All patients who received at least 1 dose of study treatment and had measurable disease at baseline according to the independent review of baseline imaging data.

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) or progression of NTLs or a new lesion. DCR is the percentage of patients with best response of CR, PR or SD (according to independent review), prior to progression (PD) or further anti-cancer therapy.

Outcome measures

Outcome measures
Measure	AZD9291 80mg n=199 Participants Daily single dose of AZD9291 80mg
Disease Control Rate (DCR)	91.5 % of participants Interval 86.7 to 94.9

SECONDARY outcome

Timeframe: RECIST tumour assessments every 6 weeks from first dose until objective disease progression, up to approximately 11 months (at the time of analysis)

Population: All patients who received at least 1 dose of study treatment.

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 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 or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST 1.1 assessment.

Outcome measures

Outcome measures
Measure	AZD9291 80mg n=210 Participants Daily single dose of AZD9291 80mg
Progression-Free Survival (PFS)	8.6 months Interval 8.28 to 9.72

Adverse Events

AZD9291 80mg

Serious events: 42 serious events

Other events: 193 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD9291 80mg n=210 participants at risk Daily single dose of AZD9291 80mg
Blood and lymphatic system disorders Anaemia	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Thrombocytopenia	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Cardiac disorders Supraventricular tachycardia	0.95% 2/210 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Ear and labyrinth disorders Hearing impaired	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Abdominal pain	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Gastritis	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Small intestinal obstruction	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
General disorders Fatigue	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
General disorders Pyrexia	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Hepatobiliary disorders Drug-induced liver injury	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Gastroenteritis	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Influenza	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Lung infection	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Pharyngeal abscess	0.48% 1/210 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Pneumonia	1.9% 4/210 • Number of events 5 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Sepsis	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Upper respiratory tract infection	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Urinary tract infection	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Injury, poisoning and procedural complications Radiation necrosis	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Dehydration	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Failure to thrive	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Cerebral haemorrhage	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Cerebral infarction	0.95% 2/210 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Headache	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Transient ischaemic attack	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.95% 2/210 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.48% 1/210 • Number of events 1 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.8% 8/210 • Number of events 9 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Vascular disorders Deep vein thrombosis	0.95% 2/210 • Number of events 2 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.

Other adverse events

Other adverse events
Measure	AZD9291 80mg n=210 participants at risk Daily single dose of AZD9291 80mg
Blood and lymphatic system disorders Anaemia	9.0% 19/210 • Number of events 19 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Blood and lymphatic system disorders Thrombocytopenia	5.2% 11/210 • Number of events 15 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Eye disorders Dry eye	5.2% 11/210 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Abdominal pain upper	5.2% 11/210 • Number of events 14 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Constipation	15.2% 32/210 • Number of events 38 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Diarrhoea	38.6% 81/210 • Number of events 115 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Nausea	16.2% 34/210 • Number of events 35 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Stomatitis	10.5% 22/210 • Number of events 31 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Gastrointestinal disorders Vomiting	7.6% 16/210 • Number of events 18 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
General disorders Asthenia	5.2% 11/210 • Number of events 12 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
General disorders Fatigue	14.8% 31/210 • Number of events 33 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
General disorders Oedema peripheral	8.1% 17/210 • Number of events 18 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Nasopharyngitis	10.0% 21/210 • Number of events 23 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Paronychia	15.2% 32/210 • Number of events 32 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Upper respiratory tract infection	5.2% 11/210 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Infections and infestations Urinary tract infection	6.2% 13/210 • Number of events 16 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations Alanine aminotransferase increased	7.1% 15/210 • Number of events 17 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations Aspartate aminotransferase increased	5.7% 12/210 • Number of events 12 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations Electrocardiogram QT prolonged	5.2% 11/210 • Number of events 13 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations Neutrophil count decreased	6.7% 14/210 • Number of events 17 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations Platelet count decreased	9.5% 20/210 • Number of events 23 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Investigations White blood cell count decreased	7.6% 16/210 • Number of events 22 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Metabolism and nutrition disorders Decreased appetite	13.8% 29/210 • Number of events 32 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Arthralgia	8.6% 18/210 • Number of events 19 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Back pain	11.9% 25/210 • Number of events 26 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 11/210 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.7% 14/210 • Number of events 15 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Musculoskeletal and connective tissue disorders Pain in extremity	6.7% 14/210 • Number of events 14 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Dizziness	5.2% 11/210 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Nervous system disorders Headache	9.5% 20/210 • Number of events 25 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Psychiatric disorders Insomnia	5.2% 11/210 • Number of events 11 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Cough	11.9% 25/210 • Number of events 31 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 14/210 • Number of events 16 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Dermatitis acneiform	7.6% 16/210 • Number of events 16 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Dry skin	24.8% 52/210 • Number of events 58 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Pruritus	15.2% 32/210 • Number of events 33 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Rash	23.3% 49/210 • Number of events 58 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Rash maculo-papular	6.7% 14/210 • Number of events 17 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.
Skin and subcutaneous tissue disorders Skin fissures	5.7% 12/210 • Number of events 18 • AEs from start of study drug until 28 days post treatment discontinuation, up to approximately 11 months (at time of analysis). Systematic assessment due to regular investigator assessment at study visits.

Additional Information

Senior Medical Director, Tagrisso

AstraZeneca

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review, should the submission for publication be delayed in order to file patent application. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER