A molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib - ELIOS

Study identifier:D5161C00003

ClinicalTrials.gov identifier:NCT03239340

EudraCT identifier:2017-002359-27

CTIS identifier:N/A

Study Complete

Official Title

A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib

Medical condition

EGFR mutation positive locally advanced or metastatic Non-Small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

Osimertinib

Sex

All

Actual Enrollment

154

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 30 May 2018

Primary Completion Date: 19 Sept 2023

Study Completion Date: 19 Sept 2023

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2024 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

1.Provision of informed consent prior
2.Patients aged 18 years or older
3.Patients with histological confirmation of locally advanced or metastatic NSCLC
4. Patients with M1 stage according to the Tumor, Node and Metastasis Classification of Malignant Tumours (TNM)
5.Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be associated with EGFR TKI sensitivity
6.Existence of measurable or evaluable disease (as per RECIST 1.1 criteria).
7.Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue
8.WHO performance status 0-1
9.Life expectancy ≥12 weeks
10.Capacity to swallow
11.Patients able to complete study and within geographical proximity allowing for adequate follow up
12.Resolution of all acute toxic effects of previous anticancer therapy
13.Female patients must be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential
14.Male patients must be willing to use barrier contraception

Exclusion Criteria

1.Locally advanced lung cancer candidate for curative treatment through radical surgery and/or radio(chemo)therapy
2.Patients diagnosed with another lung cancer subtype
3.Patients with an EGFR exon 20 insertion
4.Patients with just one measurable or evaluable tumour lesion that has been resected or irradiated prior to their enrolment in the study
5.Second active neoplasia
6.Treatment with an investigational drug within five half-lives of the compound
7.Participation in another clinical study with an investigational product (IP) during the last 3 weeks before the first day of study treatment
8.Patients who have received prior immunotherapies
9.Patients who have received prior EGFR treatments for lung cancer
10.Patients who have received prior treatment with an EGFR TKI including in the adjuvant setting
11.Patients who have received previous treatment for metastatic or stage IV disease
12.Prior treatment with cytotoxic chemotherapy for advanced NSCLC
13.Patients with a history of cancer that has been completely treated, with no evidence of malignant disease currently cannot be enrolled in the study if their chemotherapy was completed less than 6 months prior and/or have received a bone marrow transplant less than 2 years before the first day of study treatment
14.Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy
15.Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or active infection (eg, patients receiving treatment for infection) including hepatitis C and human immunodeficiency virus (HIV), or active uncontrolled Hepatitis B virus (HBV) infection.
16.Patients who have had a surgical procedure unrelated to the study within 14 days or major surgery within 1 month prior to the administration of the study drug
17.Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis
18.Any of the following cardiac criteria: Mean resting QT interval corrected for heart rate (QTc) more than 470 msec, obtained from 3 ECGs, using the screening clinic ECG machine derived QTc value. Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block and second degree heart block. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, hypomagnesaemia, hypocalcaemia, 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
19. Spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. 20.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
21.Inadequate bone marrow reserve or organ function
22.Female patients who are breastfeeding
23.Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome (CYP) 3A4.
24.Patient unwilling to undergo a biopsy at the time of disease progression
25.History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib
26.Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
27.Involvement in the planning and/or conduct of the study
28.Previous enrolment in the present study

Study design This is a phase II, open-label, single-arm tissue and plasma acquisition study assessing the efficacy, safety and underlying resistance mechanisms of osimertinib (80 mg orally, once daily) as first-line treatment in patients with locally advanced or metastatic EGFR mutation positive non-small cell lung cancer who are EGFR tyrosine kinase inhibitor treatment-naïve and eligible for first-line treatment. Participants with EGFR mutation-positive non-small cell lung cancer will be required to consent to 2 mandatory tumour biopsies to be considered for enrolment in this study. The first biopsy will be done prior to initiating treatment with osimertinib and the second biopsy will be obtained any time between Investigator assessed, Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)-defined progression and before the start of any new anticancer treatment. A third optional biopsy may be taken during the course of treatment at the Investigator’s discretion if the patient consents and if clinically feasible. Tumour tissue and plasma samples will be collected and examined for genetic and non genetic aberrations that may be important in determining response and resistance to the treatment that participants will receive as a part of their cancer care. Patients should continue on osimertinib until progression or until other treatment discontinuation criteria are met. However, if patients continue to show clinical benefit to treatment as judged by the Investigator, patients may continue to receive osimertinib beyond RECIST 1.1-defined progression. Therefore, there is no maximum duration of treatment. Tumour assessments will be performed at baseline and then every 8 weeks from study enrolment until 3.5 years, and then every 10 weeks until RECIST 1.1-defined. Patients will be followed up for a period of 28 days following discontinuation of osimertinib. Target patient population Male and female patients aged 18 years and over with locally advanced or metastatic pathologically confirmed adenocarcinoma of the lung, not amenable to curative surgery or radiotherapy. Patients will have a tumour that harbours one of the EGFR mutations known to be associated with EGFR tyrosine kinase inhibitor sensitivity, either alone or in combination with other EGFR mutations (EGFR mutation status determined by a local laboratory). Patients must be EGFR tyrosine kinase inhibitor treatment-naïve and eligible to receive first line treatment with osimertinib. Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR. Osimertinib (80 mg orally, once daily) will be administered. Doses may be reduced to 40 mg if needed.

Location

Research Site

Parma, Italy, 43126

Location

Research Site

MELDOLA, Italy, 47014

Location

Research Site

Terni, Italy, 05100

Location

Research Site

Monza, Italy, 20900

Location

Research Site

Cheongiu, Republic of Korea, 28644

Location

Research Site

Seoul, Republic of Korea, 05505

Location

Research Site

Seoul, Republic of Korea, 03722

Location

Research Site

Busan, Republic of Korea, 47392

Arms	Assigned Interventions
Experimental: Osimertinib An oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer	Drug: Osimertinib Osimertinib is an oral, potent, selective, irreversible inhibitor of both EGFR-tyrosine kinase inhibitor sensitizing and resistance mutations in non-small cell lung cancer with a significant selectivity margin over wild type EGFR. Other Name: TAGRISSO, AZD9291

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled in this study from 30 May 2018 (First subject in) and analyses presented in this results form are based on a final data cut-off of 18 July 2023 and final database lock of 15 December 2023.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants meeting eligibility criteria predefined in protocol were enrolled in the study. All the assessments were performed as per the schedule of the assessments.

Reporting Groups

	Description
Osimertinib 80mg	Participants received Osimertinib 80mg orally once daily.

Participant Flow: Overall Study

	Osimertinib 80mg
STARTED	154
COMPLETED	33
NOT COMPLETED	121
Other	26
Patients who are ongoing in the study at DCO	10
Death	40
Lost to Follow-up	2
Physician Decision	16
Withdrawal by Subject	27

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Osimertinib 80mg	Participants received Osimertinib 80mg orally once daily.

Baseline Measures

	Osimertinib 80mg
Number of Participants [units: Participants]	154
Age Continuous [units: Years] Mean ± Standard Deviation	62.7 ± 10.36
Sex: Female, Male [units: Participants]
Female	92
Male	62
Race/Ethnicity, Customized [units: Participants]
White	30
Black or African American	5
Asian	118
Other	1
Race/Ethnicity, Customized [units: Participants]
Hispanic	6
Not Hispanic or Latino	148

Outcome Measures

1. Primary Outcome Measure: Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression [ Time Frame: Genetic and proteomic markers were assessed at baseline and progression (up to 5 years after baseline) ]

Measure Type	Primary
Measure Name	Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression
Measure Description	The frequency of genetic and proteomic markers at disease progression regardless of their prevalence was evaluated.
Time Frame	Genetic and proteomic markers were assessed at baseline and progression (up to 5 years after baseline)
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The primary analysis set included all patients with evaluable paired biopsies, which were defined as follows: the first biopsy was taken prior to osimertinib treatment, and the second biopsy was taken at any time between Investigator-assessed RECIST 1.1-defined progression and before the start of any new anticancer treatment.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	51
Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression [units: Percentage of participants] Number (95% Confidence Interval)
AKT2; Copy Number Alteration: Type; amplification	2.0 (0.05 to 10.45)
ALK; Rearrangement	3.9 (0.48 to 13.46)
APC; Copy Number Alteration; Type: loss	2.0 (0.05 to 10.45)
ARAF; Copy Number Alteration; Type: amplification	3.9 (0.48 to 13.46)
ASXL1; Short Variant; Type: Q588*	2.0 (0.05 to 10.45)
ATRX; Short Variant; Type: P599fs*22	2.0 (0.05 to 10.45)
AXL; Copy Number Alteration; Type: amplification	2.0 (0.05 to 10.45)
BCL2L2; Copy Number Alteration; Type: amplification	3.9 (0.48 to 13.46)
BRAF; Rearrangement	2.0 (0.05 to 10.45)
BRAF; Short variant; Type: G469A	2.0 (0.05 to 10.45)
BRAF; Short variant Type: V600E	3.9 (0.48 to 13.46)
CBL; Short Variant; Type: R149Q	2.0 (0.05 to 10.45)
CCND1 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
CCNE1 Copy Number Alteration Type: amplification	5.9 (1.23 to 16.24)
CDK4 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
CDK6 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
CDKN1B Short Variant Type: S2*	2.0 (0.05 to 10.45)
CDKN2A Copy Number Alteration Type: loss	15.7 (7.02 to 28.59)
CDKN2A; Short Variant Type: P38L	2.0 (0.05 to 10.45)
CDKN2B Copy Number Alteration Type: loss	15.7 (7.02 to 28.59)
CRKL Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
CUL4A Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
DIS3 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
EGFR Copy Number Alteration Type: amplification	11.8 (4.44 to 23.87)
EGFR Rearrangement	2.0 (0.05 to 10.45)
EGFR Short Variant Type: C797S	7 (5.70 to 26.26)
EGFR Short Variant Type: L858R	2.0 (0.05 to 10.45)
EMSY Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
ERBB2 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
FANCG Rearrangement	2.0 (0.05 to 10.45)
FGF10 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
FGF14; Copy Number Alteration; Type: amplification	2.0 (0.05 to 10.45)
FGF19 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
FGFR1 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
FGFR3 Rearrangement	2.0 (0.05 to 10.45)
FGFR4 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
HGF Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
HRAS Short Variant Type: Q61R	2.0 (0.05 to 10.45)
IDH1 Short Variant Type: R132L	2.0 (0.05 to 10.45)
IGF1R Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
IRS2 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
KRAS Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
LYN Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
MAP2K1 Short Variant Type: E102_I103del	2.0 (0.05 to 10.45)
MCL1 Copy Number Alteration Type: amplification	5.9 (1.23 to 16.24)
MDM2 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
MET Copy Number Alteration Type: amplification	17.6 (8.40 to 30.87)
MTAP Copy Number Alteration Type: loss	13.7 (5.70 to 26.26)
MYC Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
MYCN Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
NF1 Short Variant Type: M1I	2.0 (0.05 to 10.45)
NFE2L2 Short Variant Type: D29N	2.0 (0.05 to 10.45)
NFKBIA Copy Number Alteration Type: amplification	9.8 (3.26 to 21.41)
NKX2-1 Copy Number Alteration Type: amplification	9.8 (3.26 to 21.41)
NOTCH3 Rearrangement	2.0 (0.05 to 10.45)
NTRK1 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
PARP1 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
PDGFRB Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
PIK3CA Short Variant Type: E542K	2.0 (0.05 to 10.45)
PIM1 Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
RAD21 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
RB1 Copy Number Alteration Type: loss	3.9 (0.48 to 13.46)
RB1 Short Variant Type: Q846*	2.0 (0.05 to 10.45)
RICTOR Copy Number Alteration Type: amplification	7.8 (2.18 to 18.88)
SMAD4 Rearrangement	2.0 (0.05 to 10.45)
SMAD4 Short Variant Type: W524L	2.0 (0.05 to 10.45)
SPEN Short Variant Type: D2047fs*17	2.0 (0.05 to 10.45)
STK11 Copy Number Alteration Type: loss	2.0 (0.05 to 10.45)
STK11 Short Variant Type: K269fs*18	2.0 (0.05 to 10.45)
TERC Copy Number Alteration Type: amplification	2.0 (0.05 to 10.45)
TERT Short Variant Type: promoter -146C>T	2.0 (0.05 to 10.45)
TET2 Short Variant Type: Q916*	2.0 (0.05 to 10.45)
TET2 Short Variant Type: V1862fs*13	2.0 (0.05 to 10.45)
TP53 Short Variant Type: R213*	2.0 (0.05 to 10.45)
WHSC1L1 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)
ZNF703 Copy Number Alteration Type: amplification	3.9 (0.48 to 13.46)

No statistical analysis provided for Proportion of patients with a given tumour genetic and proteomic marker at the point of disease progression

2. Secondary Outcome Measure: Progression free survival (PFS) [ Time Frame: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	Progression free survival (PFS)
Measure Description	PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression.
Time Frame	From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least one dose of Osimertinib.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	154
Progression free survival (PFS) [units: Months] Median (95% Confidence Interval)	16.4 (12.7 to 20.3)

No statistical analysis provided for Progression free survival (PFS)

3. Secondary Outcome Measure: Objective Response Rate (ORR) [ Time Frame: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years ]

Measure Type	Secondary
Measure Name	Objective Response Rate (ORR)
Measure Description	ORR is defined as the number (%) of patients with at least one visit response of complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later.
Time Frame	From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least one dose of Osimertinib.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	154
Objective Response Rate (ORR) [units: Percentage of participants] Number (95% Confidence Interval)	73.4 (65.66 to 80.17)

No statistical analysis provided for Objective Response Rate (ORR)

4. Secondary Outcome Measure: Duration of Response (DoR) [ Time Frame: From date of first documentation of complete/partial response until the date of progression, or last evaluable RECIST assessment for participants that did not progress within 2 missed visits of last assessment, up to 5 years ]

Measure Type	Secondary
Measure Name	Duration of Response (DoR)
Measure Description	Duration of response is defined as the time from the date of first documented response, (that is subsequently confirmed) 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 PFS endpoint. The time of the initial response will be defined as the latest of the dates contributing towards the first visit that was CR or PR that was subsequently confirmed.
Time Frame	From date of first documentation of complete/partial response until the date of progression, or last evaluable RECIST assessment for participants that did not progress within 2 missed visits of last assessment, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib. The Duration of response is calculated for only participants with a confirmed response. Participants must have had measurable disease at baseline to be included in the study.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	113
Duration of Response (DoR) [units: Months] Median (95% Confidence Interval)	18.8 (14.2 to 22.3)

No statistical analysis provided for Duration of Response (DoR)

5. Secondary Outcome Measure: Disease control rate (DCR) [ Time Frame: 8 weeks ]

Measure Type	Secondary
Measure Name	Disease control rate (DCR)
Measure Description	DCR is defined as percentage of patients with confirmed complete response, confirmed partial response or with stable disease.
Time Frame	8 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of osimertinib.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	154
Disease control rate (DCR) [units: Percentage of participants] Number (95% Confidence Interval)	94.8 (90.02 to 97.73)

No statistical analysis provided for Disease control rate (DCR)

6. Secondary Outcome Measure: Time to Treatment Discontinuation or Death (TTD) [ Time Frame: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	Time to Treatment Discontinuation or Death (TTD)
Measure Description	TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death.
Time Frame	From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80 mg orally once daily with epidermal growth factor receptor (EGFR).

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	154
Time to Treatment Discontinuation or Death (TTD) [units: Months] Median (95% Confidence Interval)	20.0 (16.3 to 23.8)

No statistical analysis provided for Time to Treatment Discontinuation or Death (TTD)

7. Secondary Outcome Measure: Time to first subsequent therapy or Death (TFST) [ Time Frame: From date of first dose to start of subsequent anticancer therapy or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	Time to first subsequent therapy or Death (TFST)
Measure Description	TFST is defined as the time from the date of first dose of osimertinib to the earlier of the date of anticancer therapy start date following study treatment discontinuation, or death.
Time Frame	From date of first dose to start of subsequent anticancer therapy or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80 mg orally once daily.

Measured Values

	Osimertinib 80 mg
Number of Participants Analyzed [units:participants]	154
Time to first subsequent therapy or Death (TFST) [units: Months] Median (95% Confidence Interval)	32.1 (24.0 to 47.7)

No statistical analysis provided for Time to first subsequent therapy or Death (TFST)

8. Secondary Outcome Measure: PFS in patient subgroups defined by molecular profile: Epidermal growth factor receptor (EGFR) tumor mutation at baseline [ Time Frame: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	PFS in patient subgroups defined by molecular profile: Epidermal growth factor receptor (EGFR) tumor mutation at baseline
Measure Description	PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. PFS was analysed in patient subgroups defined by molecular profile, including but not limited to: EGFR tumor mutation at baseline-Exon19del or L858R
Time Frame	From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Patient with L858R received Osimertinib 80 mg orally one daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	85	58
PFS in patient subgroups defined by molecular profile: Epidermal growth factor receptor (EGFR) tumor mutation at baseline [units: Months] Median (95% Confidence Interval)	22.0 (16.0 to 27.6)	12.9 (10.8 to 18.2)

No statistical analysis provided for PFS in patient subgroups defined by molecular profile: Epidermal growth factor receptor (EGFR) tumor mutation at baseline

9. Secondary Outcome Measure: PFS in patient subgroups defined by molecular profile: Detectable in Plasma-Derived ctDNA at baseline [ Time Frame: From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	PFS in patient subgroups defined by molecular profile: Detectable in Plasma-Derived ctDNA at baseline
Measure Description	PFS is defined as the time from first dose of osimertinib until the date of Investigator assessed Response Evaluation Criteria in Solid Tumours (RECIST) 1.1-defined progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from therapy or receives another anticancer therapy prior to progression. PFS was analysed in patient subgroups defined by molecular profile, including but not limited to: Exon19del or L858R detectable in plasma derived circulating tumour deoxyribonucleic acid (ctDNA) at baseline.
Time Frame	From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Patient with L858R received Osimertinib 80 mg orally one daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	62	46
PFS in patient subgroups defined by molecular profile: Detectable in Plasma-Derived ctDNA at baseline [units: Months] Median (95% Confidence Interval)	19.6 (12.7 to 24.0)	13.7 (9.0 to 18.2)

No statistical analysis provided for PFS in patient subgroups defined by molecular profile: Detectable in Plasma-Derived ctDNA at baseline

10. Secondary Outcome Measure: ORR in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [ Time Frame: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years ]

Measure Type	Secondary
Measure Name	ORR in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline
Measure Description	ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later. ORR was analysed in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R
Time Frame	From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	85	58
ORR in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [units: Percentage of participants] Number (95% Confidence Interval)	82.4 (72.57 to 89.77)	69.0 (55.46 to 80.46)

No statistical analysis provided for ORR in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline

11. Secondary Outcome Measure: ORR in patient subgroups defined by molecular profile: Detectable in Plasma derived ctDNA at baseline [ Time Frame: From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years ]

Measure Type	Secondary
Measure Name	ORR in patient subgroups defined by molecular profile: Detectable in Plasma derived ctDNA at baseline
Measure Description	ORR is defined as the number (%) of patients with at least one visit response of complete response or partial response that is confirmed at least 4 weeks later. ORR was analysed in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline.
Time Frame	From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	62	46
ORR in patient subgroups defined by molecular profile: Detectable in Plasma derived ctDNA at baseline [units: Percentage of participants] Number (95% Confidence Interval)	85.5 (74.22 to 93.14)	71.7 (56.54 to 84.01)

No statistical analysis provided for ORR in patient subgroups defined by molecular profile: Detectable in Plasma derived ctDNA at baseline

12. Secondary Outcome Measure: TTD in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [ Time Frame: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	TTD in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline
Measure Description	TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. TTD was analysed in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R
Time Frame	From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del 80 mg	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del 80 mg	L858R
Number of Participants Analyzed [units:participants]	85	58
TTD in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [units: Months] Median (95% Confidence Interval)	25.5 (19.6 to 32.1)	16.5 (12.1 to 21.7)

No statistical analysis provided for TTD in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline

13. Secondary Outcome Measure: TTD in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline [ Time Frame: From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years ]

Measure Type	Secondary
Measure Name	TTD in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline
Measure Description	TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. TTD was analysed in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline.
Time Frame	From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del 80 mg	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del 80 mg	L858R
Number of Participants Analyzed [units:participants]	62	46
TTD in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline [units: Months] Median (95% Confidence Interval)	24.5 (17.8 to 29.6)	16.5 (12.1 to 21.4)

No statistical analysis provided for TTD in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline

14. Secondary Outcome Measure: Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [ Time Frame: From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years ]

Measure Type	Secondary
Measure Name	Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline
Measure Description	Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions, in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline-Exon19del or L858R. A negative change denotes a reduction in target lesion size.
Time Frame	From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	83	55
Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline [units: Percentage change] Median (Full Range)	-59.68 (-100.0 to 6.5)	-54.29 (-100.0 to 7.6)

No statistical analysis provided for Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: EGFR tumor mutation at baseline

15. Secondary Outcome Measure: Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline [ Time Frame: From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years ]

Measure Type	Secondary
Measure Name	Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline
Measure Description	Tumour shrinkage is defined as the best change from baseline in the sum of diameters of target lesions, in patient subgroups defined by molecular profile: Exon19del or L858R detectable in plasma derived ctDNA at baseline. A negative change denotes a reduction in target lesion size.
Time Frame	From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The full analysis set included all patients who received at least 1 dose of Osimertinib.

Reporting Groups

	Description
Exon19del	Participants with Exon19del received Osimertinib 80mg orally once daily.
L858R	Participants with L858R received Osimertinib 80mg orally once daily.

Measured Values

	Exon19del	L858R
Number of Participants Analyzed [units:participants]	60	44
Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline [units: Percentage change] Median (Full Range)	-60.80 (-100.0 to 6.5)	-58.33 (-100.0 to 7.6)

No statistical analysis provided for Tumour shrinkage/depth of response in patient subgroups defined by molecular profile: Detectable in plasma derived ctDNA at baseline

Serious Adverse Events

Time Frame	From Day 1 to Follow-up (28 days post last dose) up to 5 years
Additional Description	No text entered.

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Serious Adverse Events

Osimertinib 80 mg

Total, serious adverse events

# participants affected / at risk

53/154 (34.42%)

Infections and infestations

COVID-19¹

# participants affected / at risk

1/154 (0.65%)

Infections and infestations

Gastroenteritis¹

# participants affected / at risk

2/154 (1.30%)

Infections and infestations

Lower respiratory tract infection¹

# participants affected / at risk

1/154 (0.65%)

Infections and infestations

Pneumonia¹

# participants affected / at risk

12/154 (7.79%)

Infections and infestations

Pneumonia aspiration¹

# participants affected / at risk

1/154 (0.65%)

Infections and infestations

Respiratory tract infection¹

# participants affected / at risk

1/154 (0.65%)

Infections and infestations

Sepsis¹

# participants affected / at risk

4/154 (2.60%)

Infections and infestations

Tuberculosis¹

# participants affected / at risk

1/154 (0.65%)

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

3/154 (1.95%)

Infections and infestations

Urosepsis¹

# participants affected / at risk

1/154 (0.65%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Cervix carcinoma¹

# participants affected / at risk

1/154 (0.65%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

1/154 (0.65%)

Blood and lymphatic system disorders

Blood loss anaemia¹

# participants affected / at risk

1/154 (0.65%)

Blood and lymphatic system disorders

Immune thrombocytopenia¹

# participants affected / at risk

1/154 (0.65%)

Endocrine disorders

Adrenal insufficiency¹

# participants affected / at risk

1/154 (0.65%)

Metabolism and nutrition disorders

Hyperglycaemic hyperosmolar nonketotic syndrome¹

# participants affected / at risk

1/154 (0.65%)

Metabolism and nutrition disorders

Hypokalaemia¹

# participants affected / at risk

1/154 (0.65%)

Metabolism and nutrition disorders

Hyponatraemia¹

# participants affected / at risk

2/154 (1.30%)

Psychiatric disorders

Confusional state¹

# participants affected / at risk

1/154 (0.65%)

Psychiatric disorders

Mania¹

# participants affected / at risk

1/154 (0.65%)

Nervous system disorders

Peripheral sensory neuropathy¹

# participants affected / at risk

1/154 (0.65%)

Nervous system disorders

Spinal cord compression¹

# participants affected / at risk

1/154 (0.65%)

Nervous system disorders

Status epilepticus¹

# participants affected / at risk

1/154 (0.65%)

Cardiac disorders

Acute coronary syndrome¹

# participants affected / at risk

2/154 (1.30%)

Cardiac disorders

Atrial fibrillation¹

# participants affected / at risk

3/154 (1.95%)

Cardiac disorders

Cardiac failure¹

# participants affected / at risk

2/154 (1.30%)

Cardiac disorders

Cardiac failure acute¹

# participants affected / at risk

1/154 (0.65%)

Vascular disorders

Deep vein thrombosis¹

# participants affected / at risk

1/154 (0.65%)

Vascular disorders

Embolism¹

# participants affected / at risk

1/154 (0.65%)

Respiratory, thoracic and mediastinal disorders

Asthma¹

# participants affected / at risk

1/154 (0.65%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

2/154 (1.30%)

Respiratory, thoracic and mediastinal disorders

Haemoptysis¹

# participants affected / at risk

1/154 (0.65%)

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹

# participants affected / at risk

2/154 (1.30%)

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹

# participants affected / at risk

2/154 (1.30%)

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹

# participants affected / at risk

1/154 (0.65%)

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹

# participants affected / at risk

1/154 (0.65%)

Gastrointestinal disorders

Duodenitis¹

# participants affected / at risk

1/154 (0.65%)

Gastrointestinal disorders

Gastritis¹

# participants affected / at risk

3/154 (1.95%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

1/154 (0.65%)

Hepatobiliary disorders

Cholecystitis¹

# participants affected / at risk

1/154 (0.65%)

Skin and subcutaneous tissue disorders

Subcutaneous emphysema¹

# participants affected / at risk

1/154 (0.65%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

1/154 (0.65%)

General disorders

Asthenia¹

# participants affected / at risk

1/154 (0.65%)

General disorders

General physical health deterioration¹

# participants affected / at risk

1/154 (0.65%)

Investigations

Platelet count decreased¹

# participants affected / at risk

1/154 (0.65%)

Investigations

Neutrophil count decreased¹

# participants affected / at risk

1/154 (0.65%)

Renal and urinary disorders

Acute kidney injury¹

# participants affected / at risk

2/154 (1.30%)

Renal and urinary disorders

Haematuria¹

# participants affected / at risk

1/154 (0.65%)

Renal and urinary disorders

Renal impairment¹

# participants affected / at risk

1/154 (0.65%)

Reproductive system and breast disorders

Vaginal haemorrhage¹

# participants affected / at risk

1/154 (0.65%)

Investigations

Electrocardiogram QT prolonged¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Femoral neck fracture¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Fibula fracture¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Foreign body aspiration¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Humerus fracture¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Pelvic fracture¹

# participants affected / at risk

1/154 (0.65%)

Injury, poisoning and procedural complications

Wound dehiscence¹

# participants affected / at risk

1/154 (0.65%)

Respiratory, thoracic and mediastinal disorders

Pulmonary embolism¹

# participants affected / at risk

4/154 (2.60%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Other Adverse Events

Time Frame	From Day 1 to Follow-up (28 days post last dose) up to 5 years
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Osimertinib 80 mg	Participants received Osimertinib 80mg orally once daily.

Other Adverse Events

Osimertinib 80 mg

Total, other (not including serious) adverse events

# participants affected / at risk

148/154 (96.10%)

Infections and infestations

COVID-19¹

# participants affected / at risk

14/154 (9.09%)

Infections and infestations

Paronychia¹

# participants affected / at risk

36/154 (23.38%)

Infections and infestations

Upper respiratory tract infection¹

# participants affected / at risk

24/154 (15.58%)

Infections and infestations

Urinary tract infection¹

# participants affected / at risk

16/154 (10.39%)

Blood and lymphatic system disorders

Anaemia¹

# participants affected / at risk

26/154 (16.88%)

Blood and lymphatic system disorders

Thrombocytopenia¹

# participants affected / at risk

9/154 (5.84%)

Metabolism and nutrition disorders

Decreased appetite¹

# participants affected / at risk

27/154 (17.53%)

Psychiatric disorders

Insomnia¹

# participants affected / at risk

10/154 (6.49%)

Nervous system disorders

Dizziness¹

# participants affected / at risk

11/154 (7.14%)

Respiratory, thoracic and mediastinal disorders

Cough¹

# participants affected / at risk

32/154 (20.78%)

Nervous system disorders

Headache¹

# participants affected / at risk

11/154 (7.14%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹

# participants affected / at risk

8/154 (5.19%)

Gastrointestinal disorders

Constipation¹

# participants affected / at risk

13/154 (8.44%)

Gastrointestinal disorders

Diarrhoea¹

# participants affected / at risk

63/154 (40.91%)

Gastrointestinal disorders

Gastritis¹

# participants affected / at risk

8/154 (5.19%)

Gastrointestinal disorders

Mouth ulceration¹

# participants affected / at risk

15/154 (9.74%)

Gastrointestinal disorders

Nausea¹

# participants affected / at risk

17/154 (11.04%)

Gastrointestinal disorders

Stomatitis¹

# participants affected / at risk

22/154 (14.29%)

Gastrointestinal disorders

Vomiting¹

# participants affected / at risk

14/154 (9.09%)

Skin and subcutaneous tissue disorders

Dermatitis acneiform¹

# participants affected / at risk

21/154 (13.64%)

Skin and subcutaneous tissue disorders

Dry skin¹

# participants affected / at risk

30/154 (19.48%)

Skin and subcutaneous tissue disorders

Pruritus¹

# participants affected / at risk

23/154 (14.94%)

Skin and subcutaneous tissue disorders

Rash¹

# participants affected / at risk

26/154 (16.88%)

Musculoskeletal and connective tissue disorders

Arthralgia¹

# participants affected / at risk

16/154 (10.39%)

Musculoskeletal and connective tissue disorders

Back pain¹

# participants affected / at risk

18/154 (11.69%)

Musculoskeletal and connective tissue disorders

Pain in extremity¹

# participants affected / at risk

10/154 (6.49%)

General disorders

Asthenia¹

# participants affected / at risk

13/154 (8.44%)

General disorders

Fatigue¹

# participants affected / at risk

11/154 (7.14%)

Investigations

Alanine aminotransferase increased¹

# participants affected / at risk

16/154 (10.39%)

Investigations

Aspartate aminotransferase increased¹

# participants affected / at risk

14/154 (9.09%)

Investigations

Gamma-glutamyltransferase increased¹

# participants affected / at risk

9/154 (5.84%)

Investigations

Platelet count decreased¹

# participants affected / at risk

11/154 (7.14%)

Investigations

Weight decreased¹

# participants affected / at risk

11/154 (7.14%)

Respiratory, thoracic and mediastinal disorders

Productive cough¹

# participants affected / at risk

9/154 (5.84%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA version 26.1

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	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 . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB. Access to this document must be restricted to relevant parties.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Redacted CSR synopsis
Download
Redacted CSP
Download
Redacted SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Zosia Piotrowska

Massachusetts General Hospital

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Redacted CSR synopsis

Redacted CSP

Redacted SAP

Trial Results Summaries