Phase I Study (Bloom) Of Azd3759, A Bbb Penetrable Egfr Inhibitor, In Egfrm Nsclc Patients With Leptomeningeal Metastasis (Lm) Who Progressed After Other Anti-Cancer Therapy.

2069Background: AZD3759 is the first EGFR inhibitor primarily designed to effectively cross the blood brain barrier (BBB) to treat central nervous system (CNS) metastases. A phase I study is ongoing to assess AZD3759 in EGFRm NSCLC patients with leptomeningeal metastasis (LM) who progressed after other treatment (NCT02228369). Methods: The primary objective is safety and tolerability, and secondary objectives include anti-tumor efficacy. Two dose levels of AZD3759, 200 mg and 300 mg BID, were assessed. Results: As of24 September, 2016,38 patients were recruited into the expansion cohorts of this phase I study. Of those, 18 were TKI pre-treated EGFRm NSCLC patients with LM. 10 and 8 patients were in the 300 and 200 mg BID cohorts, respectively. No DLTs were observed at either dose, while AZD3759 was better-tolerated at 200 than 300 mg BID during u003e 2 month treatment. The longest duration on treatment was u003e 9 months. Most common AEs included skin rash and diarrhea. 67% (12 out of 18) patients had drug-relate...