ABN401 in patients with NSCLC with MET exon 14 (METex14) skipping: Result from the pilot expansion study.
Authors: Lee Dae Ho , Han Ji-Youn , Lemech Charlotte Rose , Millward Michael , Roohullah Aflah , Choi Jun Young , Park Kyung Eui , Kim Na Young , Im Sunyhe , Rajasekaran Nirmal , Lee Sangsuk , Moon Hanlim , Hwang Sunjin , Shin YOUNGKEE , Lee Se-Hoon 
Published: June 2023

e21148

Background: c-MET alterations, specifically exon 14 skipping mutations occur in ~ 4% of NSCLC cases and are now considered an actionable biomarker in the metastatic setting1. In addition to its pathophysiological role, c-MET alterations have also been implicated as a major resistance mechanism to targeted therapies against EGFR and vascular EGFR. These findings have widened the research on c-MET-altered NSCLCs and driven a new era of MET inhibitors. ABN401, a highly selective MET kinase inhibitor, has demonstrated an acceptable safety profile and promising preliminary antitumor activity in patients (pts) with advanced solid tumors2. Here, results are reported from the pilot expansion part of phase 1 evaluating ABN401 in pts with NSCLC harboring c-MET dysregulation. Methods: Pts with c-MET dysregulation in NSCLC were enrolled in the phase 1 pilot expansion cohort. ABN401 was orally administered daily in a 21-day cycle at the recommended phase 2 dose (RP2D) of 800mg, which was established in the dose escalation cohort. The primary objective was to evaluate the safety and tolerability of ABN401 and determine the dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) according to CTCAE v5. Secondary objectives included pharmacokinetic assessments and preliminary evaluations of efficacy. Tumor assessments were performed using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) in pts with c-MET dysregulation in NSCLC. Results: c-MET dysregulated (overexpression, amplification, and METex14 skipping) NSCLC pts were enrolled and received a daily dose of 800 mg ABN401 without experiencing any dose-limiting toxicities (DLTs). As of January 31, 2023, four pts are still on treatment. The safety profile of ABN401 was consistent with previous reports2 and the most common treatment-related adverse events were nausea, vomiting, and diarrhea (grade 1, mild). All pts in this cohort tolerated the treatment well at a dose of 800mg QD. Among all, 4 pts had METex14 skipping mutations, out of which 2 pts demonstrated partial responses to the therapy, and one patient had SD. One patient with MET amplification is now in SD and has been receiving treatment for approximately 16 months. Conclusions: The ABN401 pilot expansion part of phase 1 demonstrated promising anti-tumor effects and safety in NSCLC pts with c-MET dysregulation, providing support for further evaluation of ABN401 in the METex14 skipping cohort (cohort-1) of the global phase 2 study (NCT05541822). Enrollment is currently ongoing. References National Comprehensive Cancer Network: Non-small cell lung cancer (version 2.2021). https://www.nccn.org/professionals/physician_gls/default.aspx#nscl . Dae Ho Lee, et al. Journal of Clinical Oncology 2022 40:16_suppl, 3105-3105. Clinical trial information: NCT04052971 .