Abstract 5056: ABN401 demonstrates robust anti-tumor efficacy in orthotopic PDX models of MET-driven NSCLC brain metastases in a pre-clinical study

Abstract

Abstract Background Brain metastases (BM) are manifested in approximately 30-50% of patients with non-small cell lung cancer (NSCLC) and are associated with catastrophic implications on prognosis and survival. The development of blood-brain barrier-penetrant therapies for brain metastases of NSCLC is imperative and is a major clinical hurdle. ABN401, a highly potent and selective c-MET inhibitor, shows promising anti-tumor activity without significant safety concerns in patients with advanced NSCLC. Here, we report that ABN401 exhibits potent anti-tumor efficacy in pre-clinical orthotopic patient-derived xenografts (PDXs) derived from MET-driven NSCLC brain metastases. Methods Anti-tumor efficacy of ABN401 was assessed in two lung cancer PDXs (LU5349 and LU5406) from BM models harboring high-level MET amplification grown in NOD/SCID mice. Subcutaneous PDXs (n=14/group) were treated with ABN401 (60 mg/kg QD, 125 mg/kg QD, and 165 mg/kg QD) or control groups. Established PDXs were orthotopically implanted into the brain (n=14/group) and were treated with ABN401 (125mg/kg QD), or control groups. The tumor volume of orthotopic model was monitored using magnetic resonance imaging (MRI). Brain, plasma, and tumor samples were collected for pharmacokinetics (PK) and pharmacodynamics (PD) correlation analysis. Results The efficacy of ABN401(125 mg/kg QD) was confirmed in the subcutaneous PDX models (LU5349 and LU5406). Treatment with ABN401 showed up to 95% and 99% tumor growth inhibition in the LU5349 and LU5406 models, respectively. ABN401 (125 mg/kg QD) treatment induced complete or near-complete tumor growth regressions in the orthotopic tumor model. ABN401 also showed a desirable PK and safety profile with no significant changes in body weight. Conclusions ABN401 treatment showed robust anti-tumor efficacy in PDX models of MET-driven NSCLC brain metastases. Our findings suggest that ABN401 has excellent potential for treating NSCLC patients with BM and supports its ongoing clinical development. Citation Format: Nirmal Rajasekaran, Kyung Eui Park, Saehyung Lee, Na Young Kim, Suk-Jae Chung, Young Kee Shin, Jun Young Choi. ABN401 demonstrates robust anti-tumor efficacy in orthotopic PDX models of MET-driven NSCLC brain metastases in a pre-clinical study. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5056.