EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer not amenable to curative surgery or radiotherapy MedDRA version: 20.0 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and
Conditions
Interventions
Trade Name: TAGRISSO™
Product Name: Osimertinib
Product Code: AZD9291
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Osimertinib
Current Sponsor code: AZD9291
Other descriptive name: Osi
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent prior to any study specific procedures (signed and dated informed consent form). 2. Patients aged 18 years or older. 3. Patients with histological confirmation of locally advanced or metastatic, non squamous NSCLC who are not candidates for local curative treatment. 4. Patients with M1 stage according to the Tumour, Node, and Metastasis Classification of Malignant Tumours (TNM) version 7 including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease that is not a candidate for curative treatment (including patients who progress after chemo radiotherapy in stage III disease). 5. Patients with an EGFR deletion or mutation known (from tumour biopsy or plasma) to be associated with EGFR TKI sensitivity before treatment by local assessment. 6. Existence of measurable or evaluable disease (as per RECIST 1.1 criteria). Patients with asymptomatic and stable central nervous system (CNS) metastases are eligible for the study; treatment with low dose corticosteroids is allowed, but is not a requirement for eligibility. Patients with history of CNS metastasis or compression of the spinal cord are eligible if they have received local final treatment (e.g., radiotherapy, stereotactic surgery) and if they have remained clinically stable without using anticonvulsants and increasing doses of corticosteroids for a minimum of 2 weeks prior to the first day of study treatment. 7. Possibility of obtaining sufficient tissue sample, via a biopsy or surgical resection of the primary tumour or metastatic tumour tissue, within the 60 days prior to study entry and at or after RECIST 1.1-defined progression. 8. WHO performance status 0-1. 9. Life expectancy =12 weeks. 10. Adequate coagulation: international normalised ratio (INR) =1.5 for patients on anti-coagulation therapy. 11. Capacity to swallow. 12. Patients able to complete study and within geographical proximity allowing for adequate follow up. 13. Resolution of all acute toxic effects of previous anticancer therapy (which can only be adjuvant or neoadjuvant) or surgical interventions to grade 1 according to the National Cancer Institute (NCI) CTCAE version 4.0 (except for alopecia or other side effects that the Investigator does not consider to be a risk to patient safety). 14. Female patients should be using highly effective contraceptive measures, and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of nonchildbearing potential by fulfilling one of the following criteria at screening: - Postmenopausal defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments; - Female patients under 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with luteinizing hormone and follicle stimulating hormone levels in the postmenopausal range for the institution; - Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; 15. Male patients should be willing to use barrier contraception. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 116 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 29
Exclusion criteria
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, patients with mixed NSCLC with predominantly squamous cell cancer, or with any small-cell lung cancer component. 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 (neoadjuvant/adjuvant chemotherapy is permitted if at least 6 months have elapsed between the end of chemotherapy and the first day of study treatment). 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, which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required. 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; patients with a significant traumatic lesion (as judged by the Investigator that would risk patient safety) during the 4 weeks prior to starting the administration of the study drug; patients who have not recovered from the side effects of any major surgery; or patients who might need major surgery during the course of the study. 17. Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required corticosteroid treatment, or any evidence of clinically active interstitial lung disease. 18. Any of the following cardiac criteria: - Mean resting QT interval corrected for heart rate (QTc) >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, congenital long QT syndrome, family history of long QT
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Proportion of patients with a given genetic and proteomic marker (including, but not limited to, EGFR mutations, HER2, and cMET expression and/or amplification) at the point of disease progression as defined by the Investigator;Main Objective: To examine the genetic and proteomic profile at the point of disease progression in patients receiving osimertinib as first-line EGFR TKI therapy for EGFRm+ locally advanced or metastatic NSCLC compared to the profile prior to initiation of treatment;Secondary Objective: 1) To assess the efficacy of osimertinib as first line EGFR TKI therapy for patients with EGFRm+ locally advanced or metastatic NSCLC. 2) To assess the efficacy of osimertinib in patient subgroups defined by molecular profile, including but not limited to: • Positive pre-treatment T790M mutation • EGFR Ex19del or L858R mutation • EGFR Ex19del or L858R detectable in plasma-derived circulating tumour deoxyribonucleic acid (ctDNA). 3) To further assess the efficacy of osimertinib post progression. 4) To summarize the safety and tolerability profile of osimertinib as first-line EGFR tyrosine kinase inhibitor therapy for patients with EGFR mutation-positive locally advanced or metastatic NSCLC;Timepoint(s) of evaluation of this end point: At the point of disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Throughout the trial;Secondary end point(s): Progression-free survival, according to RECIST 1.1 by Investigator assessment, and other selected clinical efficacy endpoints including: • Objective response rate • Duration of response • Disease control rate • Tumour shrinkage/depth of response, defined as best change from baseline in target lesion tumour size • Time to treatment discontinuation or death • Important patient and disease characteristics • Time to first subsequent therapy or death Safety Endpoints: • Adverse events graded by Common Terminology Criteria for Adverse Events version 4.0 • Clinical chemistry, haematology and urinalysis • Vital signs, physical examination, body weight • Electrocardiogram • World Health Organization performance status | — |
Countries
Italy, Korea, Republic of, Malaysia, Spain, Taiwan, United States
Contacts
Public ContactInformation Center
AstraZeneca
Outcome results
None listed