Abstract C036: A Phase 1 Study to assess BDTX-1535, an oral EGFR inhibitor, in patients with Glioblastoma or Non-Small Cell Lung Cancer
Authors: Yu Helena , Johnson Melissa , Henry Jason T , Spira Alex , Han Ji-Youn , Barve Minal , Battiste James , Alnahhas Iyad , Nam DoHyun , Edenfield Jeffrey , Halmos Balazs , Yoon Shinkyo , Kim Tae Min , Eathiraj Sudharshan , Hajdenberg Julio , Yurasov Sergey , Ahluwalia Manmeet , Wen Patrick 
Published: December 2023

Abstract
Background: Epidermal growth factor receptor (EGFR) is a potent oncogene commonly altered in non-small cell lung cancer (NSCLC) and glioblastoma (rGBM). For NSCLC, EGFR tyrosine kinase activity can be driven by classical driver, intrinsic driver, and acquired resistance mutations. BDTX-1535 is an orally available, highly potent, brain penetrant, selective, irreversible small molecule tyrosine kinase inhibitor that targets all 3 classes of EGFR mutations. Preclinical data demonstrated the ability of BDTX-1535 to cross the blood-brain barrier and produce sustained inhibition of EGFR signaling.
Methods: BDTX-1535-101 (NCT05256290) is a Phase 1, open-label, multicenter study to assess the safety, tolerability, pharmacokinetics (PK), central nervous system (CNS) activity, and preliminary antitumor activity of BDTX-1535 in locally advanced or metastatic NSCLC with or without CNS disease or recurrent GBM (rGBM). The primary objective is to determine the BDTX-1535 recommended Phase 2 dose (RP2D) based on the overall safety, PK, pharmacodynamic, and preliminary antitumor activity. The monotherapy dose escalation portion evaluates BDTX-1535 in patients with locally advanced/metastatic NSCLC harboring intrinsic driver EGFR mutations following standard of care or with acquired resistance EGFR mutations following a 3rd generation EGFR inhibitor in the 1st line setting, in addition to patients with rGBM expressing EGFR alterations who previously received available standard therapy of surgical resection followed by chemoradiotherapy and/or temozolomide (TMZ). A capsule-to-tablet bridging cohort and a food effect cohort will also be assessed. Following the establishment of a preliminary recommended Phase 2 dose (RP2D), the disease-specific expansion portion of the study will further evaluate the safety, tolerability, and preliminary antitumor effect of BDTX-1535. Cohorts include the following:1) advanced/metastatic NSCLC with intrinsic resistance EGFR mutations following up to 2 lines of therapy, one of which must be an EGFR inhibitor treatment, 2) advanced/metastatic NSCLC with acquired resistance EGFR mutation following a 3rd generation EGFR inhibitor in the first line setting, 3) rGBM with confirmed EGFR alterations with or without amplifications. NSCLC patients may enroll with or without CNS metastases and must not be known to express excluded resistance mutations such as EGFR T790M. BDTX-1535 will also be studied in combination with TMZ to assess safety, tolerability, and a recommended combination dose for the treatment of patients with newly diagnosed GBM harboring EGFR alterations. Enrollment was initiated in 2022 and dose escalation is almost complete. Initiation of the dose expansion cohorts of NSCLC patients with EGFR acquired resistance and intrinsic driver mutations after progression on prior EGFR inhibitor is planned for the second half of 2023. For additional information, please contact ClinicalTrials@bdtx.com.
Citation Format: Helena Yu, Melissa Johnson, Jason T Henry, Alex Spira, Ji-Youn Han, Minal Barve, James Battiste, Iyad Alnahhas, DoHyun Nam, Jeffrey Edenfield, Balazs Halmos, Shinkyo Yoon, Tae Min Kim, Sudharshan Eathiraj, Julio Hajdenberg, Sergey Yurasov, Manmeet Ahluwalia, Patrick Wen. A Phase 1 Study to assess BDTX-1535, an oral EGFR inhibitor, in patients with Glioblastoma or Non-Small Cell Lung Cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C036.