Health Condition 1: C349- Malignant neoplasm of unspecifiedpart of bronchus or lung
Conditions
Interventions
Intervention1: Osimertinib
: Savolitinib.
Total duration of therapy will be until either objective disease progression, unacceptable toxicity occurs, consent is withdrawn or another discontinuation c
Sponsors
AstraZeneca AB
Eligibility
Inclusion criteria
Inclusion criteria: 1 Patients must be more than equal to 18 years of age All genders are permitted 2 Histologically or cytologically confirmed locally advanced or metastatic EGFRm positive NSCLC harbouring an EGFR mutation known to be associated with EGFR TKI sensitivity including either exon 19 deletion and/or L858R which is not amenable to curative therapy. 3 Documented radiologic disease progression following treatment with osimertinib Osimertinib does not need to be the most recent therapy 4 MET amplification or high expression as determined by FISH central IHC central or NGS local testing on tumour tissue collected following progression on prior osimertinib treatment 5 Available tissue from a recent biopsy for MET analysis or willingness to collect additional tissue for central testing 6 At least 1 lesion not previously irradiated not biopsied during the screening period that can be accurately measured at baseline as more than equal to 10 mm in the longest diameter except lymph nodes which must have short axis more than equal to 15 mm with CT or MRI which is suitable for accurate repeated measurements 7 Received at least 1 but no more than 3 prior lines of therapy may include investigational therapy in the locally advanced/metastatic setting 8 No more than one prior line of chemotherapy regimen 9 A chemotherapy regimen including a programmed cell death-1 PD1 or a PD1 ligand 1 PD L1 agent is acceptable provided it was not the most recent line of therapy 10 No more than 2 prior lines of therapy containing EGFR TKI are acceptable 11 Adequate haematological function defined as - Absolute neutrophil count more than equal to 1500 per µL Haemoglobin more than equal to 9 g per dL no transfusion in the past 2 weeks Platelets more than equal to 100,000 per µL no transfusion in the past 10 days Adequate liver function ALT AST less than equal to 2.5 times ULN with total bilirubin less than equal to ULN OR Total bilirubin more than ULN to less than equal to 1.5 times ULN with ALT and AST less than equal to ULN Adequate renal function - creatinine less than 1.5 times the institutional ULN OR a glomerular filtration rate more than equal to 50 mL per min. Confirmation of creatinine clearance is only required when creatinine is more than 1.5 times ULN Adequate coagulation parameters INR less than 1.5 times ULN and activated partial thromboplastin time less than 1.5 times ULN unless patients are receiving therapeutic anti coagulation which affects these parameters 12 Patients with known tumour thrombus or deep vein thrombosis are eligible if clinically stable on low molecular weight heparin for more than equal to 2 weeks 13 ECOG or WHO performance status of 0 or 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks 14 Females of childbearing potential must be using highly effective contraceptive measures and have a negative pregnancy test 15 Males with a female partner of childbearing potential should be willing to use barrier contraception during the study and for 6 months following discontinuation of study drug
Exclusion criteria
Exclusion criteria: 1 Unresolved toxicities from any prior therapy greater than Common Terminology Criteria for Adverse Events CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2 prior platinum therapy related neuropathy 2 As judged by the investigator active gastrointestinal disease or other condition that will interfere significantly with the absorption distribution metabolism or excretion of oral therapy example ulcerative disease uncontrolled nausea vomiting diarrhoea Grade more than equal to 2 malabsorption syndrome or previous significant bowel resection 3 Any of the following cardiac diseases currently or within the last 6 months Unstable angina pectoris Congestive heart failure New York Heart Association NYHA more than equal to Grade 2 Acute myocardial infarction Stroke or transient ischemic attack Uncontrolled hypertension BP more than equal to 150 by 95 mmHg despite medical therapy. Mean resting correct QT interval QTcF more than 470 msec for women and more than 450 msec for men at Screening obtained from 3 ECGs using the screening clinic ECG machine derived QTcF value Any factors that may increase the risk of QTcF prolongation or risk of arrhythmic events such as heart failure chronic hypokalaemia not correctable with supplements congenital or familial long QT syndrome family history of unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes Any clinically important abnormalities in rhythm conduction or morphology of resting ECGs example complete left bundle branch block third degree heart block second degree heart block P-R interval more than 250 msec Acute coronary syndrome 4 Wide field radiotherapy including therapeutic radioisotopes such as strontium 89 administered less than equal to 28 days or limited field radiation for palliation less than equal to 7 days prior to starting study drug or has not recovered from side effects of such therapy 5 Major surgical procedures less than equal to 28 days of beginning study drug or minor surgical procedures less than equal to 7 days 6 Evidence of severe or uncontrolled systemic diseases including renal transplant active bleeding diatheses or uncontrolled hypertension which in the investigators opinion makes it undesirable for the patient to participate 7 Active hepatitis B or C 8 Known serious active infection example tuberculosis or human immunodeficiency virus 9 Presence of other active cancers or history of treatment for invasive cancer within the last 5 years Patients with Stage I cancer who have received definitive local treatment at least 3 years previously and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma ie non-invasive are eligible as are patients with history of non-melanoma skin cancer 10 Spinal cord compression or brain metastases unless asymptomatic stable and not requiring steroids for at least 2 weeks prior to start of study treatment 11 Past medical history of interstitial lung disease ILD drug-induced ILD radiation pneumonitis which required steroid treatment or any evidence of clinically active ILD 12 Inadequate bone marrow reserve or organ function as demonstrated by any
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the efficacy of savolitinib in combination with osimertinib in patients with EGFRm positive MET positive locally advanced or metastatic NSCLC who have progressed on osimertinib Determined by FISHTimepoint: 36 months after dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response by investigator assessment in accordance with RECIST 1 To determine the efficacy of savolitinib in combination with osimertinib in patients with EGFRm positive MET positive locally advanced or metastatic NSCLC who have progressed on osimertinib In patients centrally confirmed as MET positive by FISH by IHC and in all patientsTimepoint: Up to approximately 36 months after 1st patient dosed;Overall Survival by investigator assessment in accordance with RECIST 1 To determine the efficacy of savolitinib in combination with osimertinib in patients with EGFRm positive MET positive locally advanced or metastatic NSCLC who have progressed on osimertinib In patients centrally confirmed as MET positive by FISH by IHC and in all patientsTimepoint: Up to approximately 36 months after 1st patient dosed;To assess the impact of savolitinib and osimertinib on disease related symptoms and health related quality of life HRQoL in patients centrally confirmed as MET positive by FISH by IHC and in all patientsTimepoint: Up to approximately 36 months after 1st patient dosed;To determine the efficacy of savolitinib in combination with osimertinib in patients with EGFRm positive MET positive locally advanced or metastatic NSCLC who have progressed on osimertinib In patients centrally confirmed as MET positive by FISH by IHC and in all patientsTimepoint: Up to approximately 36 months after 1st patient dosed;To determine the efficacy of savolitinib in combination with osimertinib in patients with EGFRm positive MET positive locally advanced or metastatic NSCLC who have progressed on osimertinib centrally confirmed by IHC and in all patientsTimepoint: Up to approximately 36 months after 1st patient dosed;To determine the rate of ctDNA clearance after osimertinib and savolitinib treatment in patients centrally confirmed as MET positive by FISH by IHC and in all patientsTimepoint: From date of first dose until the date of first documented progression up | — |
Countries
Brazil, Canada, Chile, Denmark, France, India, Israel, Italy, Japan, Spain, Taiwan, United States of America, Viet Nam
Contacts
Public ContactMr Sandeep AV
AstraZeneca Pharma India Ltd.
Outcome results
None listed