EGFR Mutation Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Conditions
Keywords
EGFR, NSCLC, Lung Cancer, Biopsy, Molecular Profiling
Brief summary
A multicentre, open-label, single-arm, molecular profiling study of patients with EGFR mutation-positive locally advanced or metastatic NSCLC treated with osimertinib.
Detailed description
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.
Interventions
DRUGOsimertinib
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.
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | Genetic and proteomic markers were assessed at baseline and progression (up to 5 years after baseline) | The frequency of genetic and proteomic markers at disease progression regardless of their prevalence was evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years | 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. |
| Duration of Response (DoR) | 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 | 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. |
| Disease Control Rate (DCR) | 8 weeks | DCR is defined as percentage of patients with confirmed complete response, confirmed partial response or with stable disease. |
| Time to Treatment Discontinuation or Death (TTD) | From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years | TTD is defined as the time from the date of first dose of osimertinib to the earliest of treatment discontinuation or death. |
| Time to First Subsequent Therapy or Death (TFST) | 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 | 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. |
| PFS in Patient Subgroups Defined by Molecular Profile: Epidermal Growth Factor Receptor (EGFR) Tumor Mutation at Baseline | From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years | 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 |
| Objective Response Rate (ORR) | From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years | 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. |
| ORR in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years | 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 |
| ORR in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | From date of first dose until progression, or last evaluable assessment in the absence of progression, up to 5 years | 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. |
| TTD in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years | 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 |
| TTD in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | From date of first dose to treatment discontinuation or death (by any cause in the absence of recurrence), up to 5 years | 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. |
| Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years | 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. |
| Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | From date of first dose until last recorded post baseline RECIST target lesion assessment scan, up to 5 years | 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. |
| PFS in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma-Derived ctDNA at Baseline | From date of first dose until date of progression or death (by any cause in the absence of recurrence), up to 5 years | 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. |
Countries
Italy, Malaysia, South Korea, Spain, United States
Participant flow
Recruitment details
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
Participants meeting eligibility criteria predefined in protocol were enrolled in the study. All the assessments were performed as per the schedule of the assessments.
Participants by arm
| Arm | Count |
|---|---|
| Osimertinib 80mg Participants received Osimertinib 80mg orally once daily. | 154 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 40 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 26 |
| Overall Study | Patients who are ongoing in the study at DCO | 10 |
| Overall Study | Physician Decision | 16 |
| Overall Study | Withdrawal by Subject | 27 |
Baseline characteristics
| Characteristic | Osimertinib 80mg |
|---|---|
| Age, Continuous | 62.7 Years STANDARD_DEVIATION 10.36 |
| Race/Ethnicity, Customized Asian | 118 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Hispanic | 6 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 148 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 30 Participants |
| Sex: Female, Male Female | 92 Participants |
| Sex: Female, Male Male | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 40 / 154 |
| other Total, other adverse events | 148 / 154 |
| serious Total, serious adverse events | 53 / 154 |
Outcome results
Primary
Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression
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)
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | AKT2; Copy Number Alteration: Type; amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ARAF; Copy Number Alteration; Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ASXL1; Short Variant; Type: Q588* | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | HRAS Short Variant Type: Q61R | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | IDH1 Short Variant Type: R132L | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | IGF1R Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | IRS2 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NFKBIA Copy Number Alteration Type: amplification | 9.8 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NKX2-1 Copy Number Alteration Type: amplification | 9.8 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | SMAD4 Short Variant Type: W524L | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | SPEN Short Variant Type: D2047fs*17 | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ALK; Rearrangement | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | APC; Copy Number Alteration; Type: loss | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ATRX; Short Variant; Type: P599fs*22 | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | AXL; Copy Number Alteration; Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | BCL2L2; Copy Number Alteration; Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | BRAF; Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | BRAF; Short variant; Type: G469A | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | BRAF; Short variant Type: V600E | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CBL; Short Variant; Type: R149Q | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CCND1 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CCNE1 Copy Number Alteration Type: amplification | 5.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDK4 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDK6 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDKN1B Short Variant Type: S2* | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDKN2A Copy Number Alteration Type: loss | 15.7 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDKN2A; Short Variant Type: P38L | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CDKN2B Copy Number Alteration Type: loss | 15.7 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CRKL Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | CUL4A Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | DIS3 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | EGFR Copy Number Alteration Type: amplification | 11.8 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | EGFR Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | EGFR Short Variant Type: C797S | 7 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | EGFR Short Variant Type: L858R | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | EMSY Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ERBB2 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FANCG Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGF10 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGF14; Copy Number Alteration; Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGF19 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGFR1 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGFR3 Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | FGFR4 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | HGF Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | KRAS Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | LYN Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MAP2K1 Short Variant Type: E102_I103del | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MCL1 Copy Number Alteration Type: amplification | 5.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MDM2 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MET Copy Number Alteration Type: amplification | 17.6 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MTAP Copy Number Alteration Type: loss | 13.7 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MYC Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | MYCN Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NF1 Short Variant Type: M1I | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NFE2L2 Short Variant Type: D29N | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NOTCH3 Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | NTRK1 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | PARP1 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | PDGFRB Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | PIK3CA Short Variant Type: E542K | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | PIM1 Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | RAD21 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | RB1 Copy Number Alteration Type: loss | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | RB1 Short Variant Type: Q846* | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | RICTOR Copy Number Alteration Type: amplification | 7.8 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | SMAD4 Rearrangement | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | STK11 Copy Number Alteration Type: loss | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | STK11 Short Variant Type: K269fs*18 | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | TERC Copy Number Alteration Type: amplification | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | TERT Short Variant Type: promoter -146C>T | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | TET2 Short Variant Type: Q916* | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | TET2 Short Variant Type: V1862fs*13 | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | TP53 Short Variant Type: R213* | 2.0 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | WHSC1L1 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
| Osimertinib 80 mg | Proportion of Patients With a Given Tumour Genetic and Proteomic Marker at the Point of Disease Progression | ZNF703 Copy Number Alteration Type: amplification | 3.9 Percentage of participants |
Secondary
Disease Control Rate (DCR)
DCR is defined as percentage of patients with confirmed complete response, confirmed partial response or with stable disease.
Time frame: 8 weeks
Population: The full analysis set included all patients who received at least 1 dose of osimertinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg | Disease Control Rate (DCR) | 94.8 Percentage of participants |
Secondary
Duration of Response (DoR)
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Duration of Response (DoR) | 18.8 Months |
Secondary
Objective Response Rate (ORR)
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
Population: The full analysis set included all patients who received at least one dose of Osimertinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg | Objective Response Rate (ORR) | 73.4 Percentage of participants |
Secondary
ORR in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg | ORR in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | 85.5 Percentage of participants |
| L858R | ORR in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | 71.7 Percentage of participants |
Secondary
ORR in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg | ORR in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | 82.4 Percentage of participants |
| L858R | ORR in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | 69.0 Percentage of participants |
Secondary
PFS in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma-Derived ctDNA at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | PFS in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma-Derived ctDNA at Baseline | 19.6 Months |
| L858R | PFS in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma-Derived ctDNA at Baseline | 13.7 Months |
Secondary
PFS in Patient Subgroups Defined by Molecular Profile: Epidermal Growth Factor Receptor (EGFR) Tumor Mutation at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | PFS in Patient Subgroups Defined by Molecular Profile: Epidermal Growth Factor Receptor (EGFR) Tumor Mutation at Baseline | 22.0 Months |
| L858R | PFS in Patient Subgroups Defined by Molecular Profile: Epidermal Growth Factor Receptor (EGFR) Tumor Mutation at Baseline | 12.9 Months |
Secondary
Progression Free Survival (PFS)
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
Population: The full analysis set included all patients who received at least one dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Progression Free Survival (PFS) | 16.4 Months |
Secondary
Time to First Subsequent Therapy or Death (TFST)
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Time to First Subsequent Therapy or Death (TFST) | 32.1 Months |
Secondary
Time to Treatment Discontinuation or Death (TTD)
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Time to Treatment Discontinuation or Death (TTD) | 20.0 Months |
Secondary
TTD in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | TTD in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | 24.5 Months |
| L858R | TTD in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | 16.5 Months |
Secondary
TTD in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | TTD in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | 25.5 Months |
| L858R | TTD in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | 16.5 Months |
Secondary
Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | -60.80 Percentage change |
| L858R | Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: Detectable in Plasma Derived ctDNA at Baseline | -58.33 Percentage change |
Secondary
Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline
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
Population: The full analysis set included all patients who received at least 1 dose of Osimertinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg | Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | -59.68 Percentage change |
| L858R | Tumour Shrinkage/Depth of Response in Patient Subgroups Defined by Molecular Profile: EGFR Tumor Mutation at Baseline | -54.29 Percentage change |