158TiP - Open label, multi-center, prospective study to investigate the efficacy and safety of osimertinib in brain metastases from patients with EGFR T790M...

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Non-Small-Cell Lung Cancer, Locally Advanced
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter Linlin Wang
Citation Annals of Oncology (2017) 28 (suppl_2): ii52-ii55. 10.1093/annonc/mdx094
Authors L. Wang1, L. Xing2, L. Cao3, L. Wang4, X. Wang5, J. Feng6, Y. Shu7, Y. Shi8, Y. Song9, J. Yu2
  • 1Shandong Cancer Hospital, 250117 - Jinan/CN
  • 2Shandong Cancer Hospital, Jinan/CN
  • 3Anhui Provincial Hospital, Hefei/CN
  • 4Affiliated Drum Tower Hospital Nanjing University, Nanjing/CN
  • 5Qilu Hospital of Shandong University, Jinan/CN
  • 6Jiangsu Cancer Institute and Hospital, Nanjing/CN
  • 7Jiangsu Provincial People’s Hospital (The First Affiliated Hospital of Nanjing Medical University), Nanjing/CN
  • 8Cancer Institute and Hospital, Chinese Academy of Medical Sciences (CAMS), Beijing/CN
  • 9Nanjing General Hospital of Nanjing Military Command(NGH)-Jinling Hospital, Nanjing/CN

Abstract

Background

The development of EGFR-TKI have led to significant advances in patients with tumors harboring EGFR mutations (EGFRm). However, increasing incidence of central nervous system (CNS) metastasis (∼40%), including leptomeningeal metastasis (LM) and brain metastasis (BM), has been reported, particular in EGFR mutant NSCLC receiving EGFR TKI treatment. Due to limited blood brain barrier (BBB) penetration of current EGFR inhibitors (i.e. 1st generation EGFR TKIs such as gefitinib, erlotinib or icotinib and 2nd generation TKIs e.g. afatinib), these drugs can only exhibit limited efficacy on CNS metastasis. Furthermore, the acquiring resistance may commonly occur due to the development of EGFR T790M mutation. Osimertinib is a novel oral, potent and irreversible inhibitor of both EGFRm sensitizing and T790M resistance mutants. In a combined analysis from AURA (NCT01802632) and AURA2 (NCT02094261) study, the ORR of pts with CNS metastases was 56%, whilst 64% in pts without CNS metastases, demonstrating the potential benefits of osimertinib in pts with BM.

Trial design

This is an open label, multi-center, prospective study to investigate the efficacy and safety of osimertinib in pts with BM. Pts with confirmed EGFR T790M positive NSCLC who received prior therapy with an EGFR-TKI and concurrent with brain metastasis will be enrolled. All eligible patients will have access to osimertinib 80mg once-daily as long as they show clinical benefit as judged by the investigator and in the absence of discontinuation criteria. All consenting pts will be required to provide CSF and blood samples pre-treatment, 6 weeks after treatment and at PD. All pts receiving osimertinib will be followed for clinical outcomes (tumor response, survival, etc) and patient reported outcomes at baseline and every 12 weeks (± 7days investigator per RECIST 1.1 until objective disease progression, intolerant toxicity, loss of follow up). A sample size of 100 patients will provide 80% power to evaluate the treatment profile of Osimertinib and its impact on the molecular evolution. The First subject in is on 11th January, 2017.

Clinical trial identification

APOLLO Study (protocol number: NCT02972333) was released on November 23, 2016.

Legal entity responsible for the study

Jinming Yu, Shandong Cancer Hospital

Funding

AstraZeneca

Disclosure

All authors have declared no conflicts of interest.