Evaluate Safety and Tolerability of RX001 in Patients With KRAS Mutant Advanced NSCLC

An Open-label, Dose Escalation, Phase I Study to Evaluate Safety and Tolerability of RX001 in Patients With KRAS Mutant Advanced Non-small Cell Lung Cancer

This is an open-label, dose-escalation Phase I study to evaluate the safety and tolerability of RX001 monotherapy in patients with advanced KRAS mutant NSCLC. Subjects aged ≥19 years with advanced NSCLC with KRAS mutations will be enrolled. Based on the investigator's judgment of the lung tumor location, RX001 will be administered as a single intratumoral treatment via bronchoscopy or CT-guided percutaneous injection. Additionally, after conducting safety, tolerability, and preliminary anti-tumor efficacy assessments for all subjects up to Week 12 (D84) following IP administration, the collected data will be reviewed by the SRC for a comprehensive evaluation. If the IP is designated for long-term follow-up studies, monitoring for malignant tumor formation and other SAEs specified by the Ministry of Food and Drug Safety (MFDS) will be conducted for a minimum of 5 years.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: RX001

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kyoungmi Jung, PhD, Seoul; Phone Number: 82 2-400-8890; Email: kmjung@genecraft.co.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
    • Contact: Lee, Professor; Phone Number: 82 02 2030-7521; Email: kyleemd@kuh.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged ≥19 years, male or female
• Subject with histologically and/or cytologically confirmed, unresectable advanced NSCLC for radical cure that are confirmed as PD for the standard of care currently known to have clinical benefits, or for which no currently available standard of care exists due to intolerance, ineligibility, treatment refusal, etc.
• Subjects must have at least one evaluable and injectable lesion as assessed on CT images based on RECIST version 1.1.
• Subjects with valid biopsy results documented the presence of KRAS mutation.
• Subjects with an ECOG performance status of 0 or 1 and an expected survival of at least 12 weeks at the time of study participation.
• Subjects with adequate hematologic and terminal organ function.
• Subjects must voluntarily sign an informed consent form approved by the IRB. Subjects must have the willingness and ability to comply with all procedures required by the protocol.

Exclusion Criteria:

• Subjects must not meet any of the following conditions:

• Subjects with a history of or current comorbidities including:

  1. Hematologic malignancies, such as lymphoma, or any other malignant tumors apart from the indication of this study.
  2. Subjects with the cardiovascular conditions such as unstable angina and/or myocardial infarction within 1 year prior to screening
  3. Subjects with the pulmonary baseline conditions:
  4. Blood coagulation disorder
  5. Active bleeding disorders (including gastrointestinal bleeding)
• Subjects who have received antithrombotics, including antiplatelets or anticoagulants
• Subjects who have received anticancer therapies within 28 days prior to trial participation, or who have not recovered or stabilized from all AEs caused by such treatments to baseline levels
• Subjects who have received radical radiotherapy within 6 weeks prior to trial participation etc.
• Subjects who have received live vaccines or attenuated vaccines within 4 weeks prior to study participation
• Subjects with active HBV or HCV, or HIV positive
• Subjects with severe infections requiring antibiotics, antifungal agents, or antiviral agents, or those with uncontrolled active infectious diseases
• Subjects with any form of primary immunodeficiency or active autoimmune diseases
• Subjects who have previously received intratumoral therapy for the target lesion
• Ineligibility or inability to participate in the study at the investigator's discretion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RX001	Drug: RX001; Subjects will receive a single RX001 (AAV-hRUNX3) treatment via Intra-tumoral injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related serious adverse event (SAE) rate	Incidence of SAEs throughout the study SAE: an adverse event or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: Death or a life-threatening adverse event Inpatient hospitalization or prolongation of existing hospitalization A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions A congenital anomaly/birth defect Any other important medical event that does not fit the criteria above but, based upon appropriate medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent one of the outcomes listed above	Observation for 12 weeks following a single dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	* ORR = percentage of participants with complete response + partial response.; Complete response (CR): Disappearance of all target lesions.; Partial response (PR): At least a 30% decrease in the diameters of target lesions, taking as reference the baseline diameters.	Observation for 12 weeks following a single dose
Progression-free survival (PFS)	PFS is defined as the time from date of treatment initiation to disease progression or death from any cause, whichever occurs first.	Observation for 12 weeks following a single dose
Target Tumor Size	Changes in the maximum length of the target lesion	Observation for 12 weeks following a single dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response assessment	Evaluate the formation of anti-AAV2 antibodies	Observation for 12 weeks following a single dose
Viral Shedding Profile Assessment	Assess the extent of vector DNA shedding in saliva, urine, feces, and other excreta following administration	Observation for 12 weeks following a single dose

Collaborators and Investigators

• Sponsor: GeneCraft Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 2, 2025
• First Submitted That Met QC Criteria: April 11, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 17, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; AAV; KRAS; RUNX3
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: GC-LCP1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The current position is "No" due to pending internal policy decisions. However, revision of internal regulations is under review to allow for potential future data sharing and registry compliance.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No