Abstract
BACKGROUND
Osimertinib is an oral, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor activating mutation (EGFRm) and the resistance mutation (T790M) that is FDA approved for patients with EGFR mutant lung cancer. The synergism between Osimertinib and radiation likely enhances DNA damage, leading to increased cell apoptosis. For patients with EGFR positive NSCLC with brain metastases, we hypothesize that the combination of Osimertinib and SRS will lead to better long term control of brain metastases as well as the systemic disease.
METHODS
This is an open label, single arm, phase I multi-institution study. It will employ a 3 + 3 design. After enrollment onto the study, patients will be started on Osimertinib at the predetermined level daily for 0–7 days, after which all patients will undergo radiosurgery and then receive Osimertinib daily concurrently until disease progression, withdrawal or until unacceptable toxicity. SRS will be given in single fraction as determined by the treating radiation oncologist and neurosurgeon.
RESULTS
Primary endpoint include Safety, tolerability and maximum tolerated dose (MTD) of Osimertinib, when administered in combination with SRS in patients with EGFR positive NSCLC with brain metastases. Secondary endpoints include Six-month intra-cranial and extra-cranial progression-free survival (PFS-6), overall survival, overall response rate, both intracranial and extra cranial in patients with EGFR positive NSCLC brain metastases.
CONCLUSION
This is an ongoing clinical trial.