NCT03257124

Study of AZD9291 in NSCLC Patients Harboring T790M Mutation Who Failed EGFR TKI and With Brain and/or LMS

Status unknown Phase 2 Last updated 16 August 2021

What this trial tests

Phase 2 trial testing AZD9291 in Non-Small Cell Lung Cancer With EGFR T790M Mutation in 80 participants. Status unknown.

Timeline

8 May 2017

Primary endpoint
31 August 2019

31 December 2021

Quick facts

Lead sponsor	Samsung Medical Center
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	80
Start date	8 May 2017
Primary completion	31 August 2019
Estimated completion	31 December 2021
Sites	1 location across South Korea

Drugs / interventions tested

• AZD9291 — full drug profile →

Conditions studied

• Non-Small Cell Lung Cancer With EGFR T790M Mutation — all drugs for Non-Small Cell Lung Cancer With EGFR T790M Mutation →
• With Brain and/or Leptomeningeal Metastasis — all drugs for With Brain and/or Leptomeningeal Metastasis →
• Failed Tyrosine Kinase Inhibitors — all drugs for Failed Tyrosine Kinase Inhibitors →

Sponsor

Samsung Medical Center

Who can join

18 and older, any sex, with Non-Small Cell Lung Cancer With EGFR T790M Mutation or With Brain and/or Leptomeningeal Metastasis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

AZD9291 is an oral potent irreversible EGFR TKI selective for sensitizing EGFR mutation and T790M resistance mutation but sparing wild-type EGFR. Preclinical studies indicate that AZD9291 has significant exposure in the brain and activity against EGFR mutant brain metastasis. In addition, anti-tumor activities of AZD9291 in patients with advanced stage EGFR mutant NSCLC including patients with brain metastasis have been reported in an ongoing Phase I study. More recently, AZD9291 at a dose of 160mg also showed promising efficacy in heavily pre-treated patients with leptomeningeal disease from EGFR mutant NSCLC. Among 11 evaluable for response, 6 patients had LM imaging improvement and 3 out of 7 patients with abnormal neurological exam at baseline had symptomatic improvement. Compared to AZD9291, other 3rd generation EGFR TKIs, rociletinib or HM61713 has not been reported to be effective in most of CNS disease of NSCLC. Further, previous studies with AZD9291 showed anecdotal case series or undetermined for T790M mutation status, indicating more systematic study is warranted.

Based on these data, the investigators are going to conduct phase II study of AZD9291 in NSCLC patients harboring T790M mutation who failed EGFR TKIs and brain and/or leptomeningeal metastasis.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A phase II, multicenter, two cohort study of 160 mg osimertinib in EGFR T790M-positive non-small-cell lung cancer patients with brain metastases or leptomeningeal disease who progressed on prior EGFR TKI therapy.
   Park S, Lee MH, Seong M, Kim ST, et al · · 2020 · cited 135× · PMID 32634610 · DOI 10.1016/j.annonc.2020.06.017
2. Liquid biopsy in central nervous system metastases: a RANO review and proposals for clinical applications.
   Boire A, Brandsma D, Brastianos PK, Le Rhun E, et al · · 2019 · cited 119× · PMID 30668804 · DOI 10.1093/neuonc/noz012
3. The Role of Microglia in Brain Metastases: Mechanisms and Strategies.
   Feng Y, Hu X, Zhang Y, Wang Y. · · 2024 · cited 27× · PMID 37307835 · DOI 10.14336/ad.2023.0514
4. Cell-Free Circulating Tumour DNA Blood Testing to Detect <i>EGFR</i> T790M Mutation in People With Advanced Non-Small Cell Lung Cancer: A Health Technology Assessment.
   Ontario Health (Quality) . · · 2020 · cited 16× · PMID 32206157
5. Diagnostic accuracy of MR imaging of patients with leptomeningeal seeding from lung adenocarcinoma based on 2017 RANO proposal: added value of contrast-enhanced 2D axial T2 FLAIR.
   Seong M, Park S, Kim ST, Park SG, et al · · 2020 · cited 14× · PMID 32897466 · DOI 10.1007/s11060-020-03617-2
6. Novel Therapeutic Approaches in Neoplastic Meningitis.
   Khosla AA, Saxena S, Ozair A, Venur VA, et al · · 2022 · cited 8× · PMID 36612116 · DOI 10.3390/cancers15010119
7. Improving outcomes for brain metastases in EGFR mutated NSCLC.
   Carlisle JW, Ramalingam SS. · · 2019 · cited 6× · PMID 32038914 · DOI 10.21037/tlcr.2019.05.08
8. Current status and perspectives of interventional clinical trials for brain metastases: analysis of ClinicalTrials.gov.
   Tini P, Marampon F, Giraffa M, Bucelli S, et al · · 2023 · cited 4× · PMID 37016421 · DOI 10.1186/s13014-023-02243-2