VRN110755: A next-generation non-covalent EGFR tyrosine kinase inhibitor for EGFR-mutated NSCLC
Presenter: Hong-ryul Jung, PhD Session: Late-Breaking Research: Clinical Research 3 Time: 4/21/2026 2:00:00 PM → 4/21/2026 5:00:00 PM
Authors
Hong-ryul Jung 1 , Tsung-Ying Yang 2 , Byung-Yong Shim 3 , Chia-Chi Lin 4 , Myung-Ju Ahn 5 , Daekwon Kim 1 1 Voronoi, inc., Incheon, Korea, Republic of, 2 Taichung Veterans General Hospital, Taichung, Taiwan, 3 St. Vincent’s Hospital, Suwon, Korea, Republic of, 4 National Taiwan University Hospital, Taipei, Taiwan, 5 Hanyang University, Seoul, Korea, Republic of
Abstract
Background: Despite the availability of multiple EGFR tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC), durable disease control remains limited by the emergence of resistance mutations. Covalent third-generation EGFR TKIs lose inhibitory activity in the presence of the C797S mutation, representing a major unmet clinical need. VRN110755 is a novel, long-resident non-covalent EGFR TKI designed to retain high potency across common and uncommon activating EGFR mutations while maintaining activity against resistance mutations. Methods: This ongoing Phase 1a dose-escalation study evaluated the safety, pharmacokinetics (PK), and preliminary antitumor activity of VRN110755 administered orally at doses up to 480 mg. For exploratory subgroup analysis, patients with EGFR C797S-positive tumors were identified by local molecular testing performed within three months prior to Cycle 1 Day 1 or by central circulating tumor DNA (ctDNA) analysis. Molecular responses were assessed longitudinally using plasma ctDNA. Results: At the data cutoff, no dose-limiting toxicities were observed at doses up to 480 mg. VRN110755 demonstrated a favorable safety profile relative to the established safety profile of approved-dose osimertinib. Among seven patients with confirmed EGFR mutations including C797S, six achieved a partial response (PR), corresponding to a confirmed objective response rate of 85.7%. Molecular response assessment demonstrated ctDNA reduction in all five evaluable patients, with complete ctDNA clearance observed in four. PK analysis showed dose-proportional systemic exposure, with plasma concentration exceeding the IC 90 for relevant EGFR mutations beginning at 160 mg, supporting a robust pharmacokinetic-pharmacodynamic relationship consistent with observed clinical activity. Conclusion: VRN110755 demonstrates promising clinical activity and a favorable safety profile in patients with EGFR-mutated NSCLC, including those harboring resistance-associated EGFR alterations. By targeting key resistance mechanisms while maintaining high potency against activating EGFR mutations, VRN110755 represents a promising next-generation EGFR inhibitor. These findings support further clinical evaluation of VRN110755 both following failure of third-generation EGFR TKIs and in earlier lines of therapy.
Disclosure
H. Jung, VORONOI, inc. Employment. T. Yang, Voronoi, inc. ). B. Shim, Voronoi, inc. ). C. Lin, Voronoi, inc. ). M. Ahn, AstraZeneca, BMS, MSD, Lilly, Merck, ONO, Roche, TAKEDA,YUHAN, Amgen Other, Honoraria. AstraZeneca, BMS, ONO, Takeda, Lilly, Merck, MSD, Amgen, Novartis, Roche, YUHAN, Arcus, Pfizer, Daichi-Sankyo, Genexin, VORONOI Other, Consultant. D. Kim, Voronoi, inc. g., Board of Directors, non-salaried role).
Cited in
Control: 10606 · Presentation Id: 11374 · Meeting 21436