Abstract B042: Efficacy and safety outcomes of ABN401 in NSCLC patients with MET Exon 14 Skipping: A clinically relevant subgroup analysis
Authors: Lee Se-Hoon , Han Ji-Youn , Lee Ki Hyeong , Lee Gyeong-Won , Lemech Charlotte , Millward Michael , Roohullah Aflah , Le Xiuning , Park Keunchil , Choi Jun Young , Kim Na Young , Im Sunyhe , Rajasekaran Nirmal , Park Kyung Eui , Lee Sangsuk , Moon Hanlim , Hwang Sunjin , Shin YoungKee , Lee Dae Ho 
Published: December 2023

Abstract
Background: In non-small-cell lung cancer (NSCLC), approximately 3-4% of patients exhibit MET exon 14 skipping (METex14) mutations. ABN401, a selective type I MET kinase inhibitor, has demonstrated promising antitumor activity and safety in advanced solid tumor patients. Here, we report updated outcomes of ABN401, focusing on METex14 NSCLC patients.
Methods: Patients enrolled in the ABN401 Phase I (NCT04052971) and Phase II (NCT05541822) trials were analyzed. The safety population consists of all patients who have been dosed at ABN401 800 mg QD, while the efficacy population comprises METex14 NSCLC patients dosed at 800 mg QD. The primary objective for phase I study was safety, and for phase II study was the objective response rate (ORR) in patients. Secondary objectives include recommended dose and regimen of ABN401, PK and preliminary efficacy of ABN401 for phase I and duration of response (DOR), objective disease control rate (DCR), progression free survival (PFS), overall survival (OS), PK, safety, and tolerability of ABN401 for phase II.
Results: Between June 23, 2022, and July 6, 2023, a total of 24 patients received ABN401 800 mg QD, including 17 METex14 NSCLC patients. Of 24 patients evaluable for safety, 2 (8.3%) experienced grades ≥3 treatment-related adverse events (TRAE). The most common treatment-related adverse events were nausea (70.8%), vomiting (29.2%), and diarrhea (33.3%). Grade ≥3 treatment-emergent adverse events occurred in 5/24 (20.8%) patients. Treatment-related adverse events leading to permanent discontinuation occurred in 0% (0/24) of patients. Peripheral edema was observed in 29.2% (grade 1-2) and there was no grade 3 or greater event in all safety evaluable populations, and 17.6% (grade 1-2) and 0% (grade 3) in METex14 NSCLC population. For the 17 METex14 NSCLC patients, one was not evaluable because the patient did not had the first tumor assessment at the time of DCO. The median age is 69 (41-81) and 70.6% were male, with 1 (0-3) as the median prior lines of treatment. 41.2% of 17 patients were ex-smoker and 58.8% were non-smoker. All patients were MET inhibitor naïve. The objective response rate was 56.2% (9/16) in the evaluable population. Overall (n = 9), 66.7% is treatment-naïve patients (n = 6). The median duration of treatment was 5.4 months for all who dosed 800 mg QD as of the data cut-off on July 6, 2023. At the time of DCO, data is not mature enough for PFS and DoR.
Conclusions: ABN401 has shown promise in antitumor efficacy and favorable toxicity in patients with locally advanced or metastatic METex14 NSCLC. The phase 2 multicenter, open-label trial (NCT05541822) is actively enrolling in the US, South Korea, and Taiwan.
Citation Format: Se-Hoon Lee, Ji-Youn Han, Ki Hyeong Lee, Gyeong-Won Lee, Charlotte Lemech, Michael Millward, Aflah Roohullah, Xiuning Le, Keunchil Park, Jun Young Choi, Na Young Kim, Sunyhe Im, Nirmal Rajasekaran, Kyung Eui Park, Sangsuk Lee, Hanlim Moon, Sunjin Hwang, YoungKee Shin, Dae Ho Lee. Efficacy and safety outcomes of ABN401 in NSCLC patients with MET Exon 14 Skipping: A clinically relevant subgroup analysis [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 B042.