Open-label PET Study with [11C]osimertinib in Patients with EGFRm NSCLC and Brain Metastases - ODIN-BM

Exclusion Criteria

• 1. Participation in another clinical study with an IP during the previous 14 days (or longer, depending on characteristics of agents used).
• 2. Treatment with any of the following: EGFR-TKI (e.g. erlotinib, gefitinib or afatinib) within 10 days or at least 5x the half-life, whichever is the longer; any cytotoxic chemotherapy, investigational agents or other anticancer drugs within 14 days of start of IP; osimertinib in the present or other studies; major surgery (excluding placement of vascular access) within 4 weeks of start of IP; radiotherapy (including brain) with a limited field of radiation within 1 week of start of IP, except in patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks of the first administration of the IP; current receipt (or inability to stop at least 3 weeks before study start) medications or herbal supplements known to be potent inducers of CYP3A4.
• 3. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting the IP with the exception of alopecia and grade 2, prior platinum therapy-related neuropathy.
• 4. History of brain surgery or major brain trauma in the last year (if the surgery is in the same hemisphere as the brain metastasis).
• 5. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses or active infection including hepatitis B, hepatitis C and HIV.
• 6. Any of the following cardiac criteria:
• - Mean resting corrected QT interval (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 (eg, complete left bundle branch block, third degree heart block, second degree heart block).
• - Patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as electrolyte abnormalities including:
• ⁃ Serum/plasma potassium
• ⁃ Serum/plasma magnesium
• ⁃ Serum/plasma calcium
• - Heart failure, 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 and cause Torsades de Pointes.
• 7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• 8. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• • ANC <1.5 × 109/L; Platelets <100 × 109/L; Haemoglobin <90 g/L;
• • Alanine aminotransferase (ALT) >2.5x ULN or >5x ULN in the presence of liver metastases;
• • Aspartate aminotransferase (AST) >2.5x ULN or >5x ULN in the presence of liver metastases;
• • Total bilirubin >1.5x ULN or >3x ULN in the presence of liver metastases or Gilbert’s Syndrome;
• • Creatinine >1.5xl ULN concurrent with creatinine clearance <50 mL/min (using Cockcroft-Gault formula).
• 9. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the tablet or previous significant bowel resection that would preclude adequate absorption of osimertinib.
• 10. History of hypersensitivity to active or inactive excipients of osimertinib or drugs with a similar chemical structure or class to osimertinib.
• 11. In addition, the following is considered a criterion for exclusion from the exploratory genetic research:
• • Previous allogenic bone marrow transplant
• • Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection
• 12. Patients on anticoagulant treatment.
• 13. Absence of collateral flow between ulnar and radial artery as assessed by the Allen´s test”.
• 14. Suffering from claustrophobia and/or having implanted metal devices or implants such as pacemaker, vascular or heart valves or metal deposits such as bullets, shells, metal grains in the eyes.
• 15. Previous participation in a research PET or PET/CT study.
• 16. The following are exclusion criteria for contrast enhanced MRIs:
• • Glomerular filtration rate <30 ml/min
• • History of renal insufficiency
• • Pregnancy
• 17. Women who are breast-feeding.