None listed
Conditions
Interventions
Drug : Each subject will receive daily osimertinib treatment for a minimum of 9 weeks, followed by surgery. Each neoadjuvant treatment cycle will last 21 days (3 weeks) except for the optional cycle 4
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Informed consent 1. Be willing and able to provide written informed consent for the trial prior to any study specific procedures. The subject must also provide consent for correlative translational study. Age and sex 2. Male or female subjects who are =18 years of age (= 19 years of age in South Korea) on the day of signing the informed consent. Type of patient and disease characteristics 3. Histologically or cytologically documented non-squamous NSCLC with completely resectable (Stage II-III) disease (according to Version 8 of the American Joint Committee on Cancer [AJCC]). Note: thick needle biopsy of endobronchial ultrasound (EBUS)/bronchoscopy is acceptable. 3a. Patients with oligometastatic disease (e.g., 1-3 brain metastases or a single adrenal metastasis with no mediastinal involvement) who are receiving definitive treatment, including surgery for the lung tumor, may be included in the trial. 4. Complete surgical resection of the primary NSCLC must be deemed achievable, as assessed by a multi-disciplinary team (MDT) evaluation (which should include a thoracic surgeon, specialised in oncologic procedures). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at enrolment, with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. 6. Lung function test results allowing curative surgery by thoracic surgeon’s assessment. 7. Cardiac function by ECHO cardiography results allowing curative surgery by thoracic surgeon’s assessment. 8. Have adequate normal organ and marrow function, including the following: • Absolute neutrophil count =1.5×109/L. • Platelet count = 100×109/L. • Haemoglobin = 9.0 g/dL. Note: The use of granulocyte colony stimulating factor (G-CSF) support, platelet transfusion and blood transfusions to meet these criteria is not permitted within the two weeks prior to the relevant blood test. • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal (ULN). • Total bilirubin (TBL) =1.5 times the ULN or for patients with documented/suspected Gilbert's disease, Total bilirubin =2 times the ULN. • Creatinine =1.5 times the ULN or creatinine clearance =50 mL/min (creatinine clearance can be measured or calculated by Cockcroft and Gault equation). If neoadjuvant chemotherapy is part of the neoadjuvant treatment regimen , calculated creatinine clearance must be =60 mL/min. 9. Body weight >30 kg. 10. Life expectancy of >6 months prior to enrolment. Tumour sample requirements 11. A tumour which harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations (ie, T790M, G719X, , S7681 and L861Q). Exon 20 insertion co-mutation are not permitted Reproduction 12. Female patients who are not abstinent (in line with the preferred and usual lifestyle choice of the patient) and intend to be sexually active with a male partner must use highly effective contraceptive measures. Women of child-bearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required prior to the first dose of any study treatment if they are of child-bearing potential; or must have evidence of non-child-bearing potential by fulfilling 1 of the following criteria at screening: • Post-me
Exclusion criteria
Exclusion criteria: Medical conditions 1. Known active infection with hepatitis C virus (HVC) or tuberculosis. Patients positive for HCV antibody are eligible only if the polymerase chain reaction is negative for HCV RNA. Screening for chronic conditions is not required. 2. Known active or uncontrolled infection with hepatitis B virus (HBV) (i.e., known positive HBV surface antigen [HBsAg] result). Participants with HBV infection may be included only if they meet all the following criteria: • Demonstrated absence of HCV co-infection or history of HCV co-infection • Demonstrated absence of HIV infection Participants with active HBV infection are eligible if they are: o Receiving anti-viral treatment for at least 6 weeks prior to study treatment o HBV DNA is suppressed to 6 months have had transaminases levels below ULN and HBV DNA levels below 350 cells/µL o No history of AIDS-defining opportunistic infection within the past 12 months o Stable for at least 4 weeks on the same anti-HIV medications 4. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically significant ILD. 5. A history of another primary malignancy, except for the following: • Malignancy treated with curative intent and with no known active disease =3 years before the first dose of osimertinib and of low potential risk for recurrence • Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease • Adequately treated carcinoma in situ without evidence of disease. • Adequately treated cancer with a very low risk of recurrence (e.g. low grade prostate cancer or low grade RCCa) may be included at a shorter interval than 3 years after discussion with the sponsor. 6. Has pre-operative radiotherapy treatment as part of the care plan. 7. Refractory nausea and vomiting, chronic gastrointestinal diseases causing inability to swallow osimertinib, or previous significant bowel resection that would preclude adequate absorption of osimertinib. 8. Mixed small cell and NSCLC histology. 9. T4 tumours infiltrating the aorta, the oesophagus and/or the heart; and/or any bulky N2 disease. 10. Any of the following cardiac criteria: • Mean resting corrected QT interval (QTc) > 470 msec obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine-derived QTcF value • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, e.g., complete left bundle branch block, second-degree heart block, and third-degree heart block • Patient with any factors that increase the risk of QTc prolongation or risk of arrhyt
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Identification of mechanisms of resistance to osimertinib (alone or in combination with chemotherapy), based on assessment of the post-Osimertinib surgical specimens. | — |
Secondary
| Measure | Time frame |
|---|---|
| Rate of pathological complete response (pCR) and of major pathologic response (MPR; i.e., 10% or less viable tumour cells);Rate of pathologic downstaging;Event-free survival (EFS; defined as time to disease recurrence or death of any cause) of treated patients;Overall survival (OS) of treated patients.;Rate of R0 resection;One-, 3- and 5-year OS rate of treated patients;One-, 3- and 5-year EFS rate of treated patients | — |
Countries
Korea, Republic of
Contacts
Public ContactYuri Kang
Yonsei University Health System, Severance Hospital
Outcome results
None listed