A first-in-human, intra-tumoral AAV2-RUNX3 gene therapy (RX001) for advanced KRAS-mutant NSCLC (NCT06934590): Phase 1 trial in progress
Presenter: Kyoungmi Jung, PhD Session: Phase I Clinical Trials in Progress Time: 4/20/2026 9:00:00 AM → 4/20/2026 12:00:00 PM
Authors
Hee Joung Kim 1 , Sung Yong Lee 2 , Jung Seop Eom 3 , Dongil Park 4 , Kyoungmi Jung 5 , You-Soub Lee 5 , Hongseok Ji 5 , Suk-Chul Bae 5 , Kye Young Lee 1 1 Medicine Lung Cancer Center, Konkuk University Medical Center, Seoul, Korea, Republic of, 2 Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea, Republic of, 3 Department of Internal Medicine, Pusan National University Hospital, Pusan, Korea, Republic of, 4 Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Korea, Republic of, 5 GeneCraft Co., Seoul, Korea, Republic of
Abstract
Background: RUNX3 is a key tumor suppressor frequently silenced in KRAS-mutant non-small cell lung cancer (NSCLC), where its loss contributes to aberrant differentiation and tumor progression. In preclinical models, restoration of RUNX3 expression regressed the oncogenic KRAS-driven NSCLC cells. RX001 is a recombinant AAV2 vector encoding RUNX3 (rAAV2-RUNX3) designed for direct intra-tumoral (IT) administration to restore RUNX3 expression within the tumor microenvironment and inhibit tumor growth. This first-in-human Phase 1 study evaluates the safety, feasibility, and biological activity following IT administration of RX001. Methods: This is open-label, multicenter, dose-escalation Phase 1 trial (NCT06934590) conducted at four sites in the Republic of Korea. Eligible patients are adults with unresectable or metastatic KRAS-mutant NSCLC who have progressed after standard systemic therapies and who have at least one lesion suitable for IT injection. RX001 is administered as a single IT dose on Day 1 across three dose levels using a standard 3+3 design. Safety monitoring includes assessment of dose-limiting toxicities, evaluation of acute and delayed AAV-related toxicities, and determination of the recommended Phase 2 dose. Endpoints : The primary endpoint is the incidence of treatment-related serious adverse events (SAEs). Key secondary endpoints include objective response rate (ORR) and change in target tumor size. Eligibility: Key inclusion criteria include histologically confirmed KRAS-mutant NSCLC, prior receipt of appropriate standard therapies, ECOG performance status 0-1, and adequate organ function. Exclusion criteria include prior receipt of intra-tumoral therapy and uncontrolled autoimmune or immune-mediated conditions. Correlative Studies: Correlative analyses will evaluate immune responses following AAV administration, including anti-AAV antibodies, CD4/CD8 T-cell activation, and IFN-γ levels in peripheral blood. Viral shedding will also be monitored in multiple clinical specimens. Trial Status: The trial is open as of September 2025, with enrollment ongoing across all sites.
Disclosure
H. Kim, None.. S. Lee, None.. J. Eom, None.. D. Park, None. K. Jung, GeneCraft Co. Employment. Y. Lee, GeneCraft Co. Employment. H. Ji, GeneCraft Co. Employment. S. Bae, GeneCraft Co. Employment. K. Lee, None.
Cited in
Control: 9850 · Presentation Id: 12193 · Meeting 21436