An Open-Label, Single-Arm, Dose-Escalation Phase I Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of EDB-102 in Patients With EGFR L858R-Mutant, Third-Generation TKI-Resistant Advanced Non-Small Cell Lung Cancer With Liver Metastases

NCT07461727 | Not Yet Recruiting Phase 1

• 1 other identifier: NCC6018/NCCH6018
• Study Type: interventional
• Target: 15
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and preliminary efficacy of EDB-102 Injection in patients with advanced non-small cell lung cancer (NSCLC) who have liver metastases. The study specifically targets patients harboring the EGFR-L858R mutation who have disease progression after treatment with third-generation EGFR tyrosine kinase inhibitors (TKIs, e.g., osimertinib). EDB-102 is a novel in vivo gene-editing therapy. It consists of CRISPR-Cas9 mRNA and a single-guide RNA (sgRNA) encapsulated in lipid nanoparticles (LNPs). The drug is designed to specifically identify and disrupt the mutant EGFR-L858R gene in tumor cells, thereby inhibiting tumor growth. Due to the liver-targeting properties of the LNP carrier, this therapy is particularly aimed at patients with liver metastases. This is a Phase I, open-label, dose-escalation study. Participants will receive a single intravenous (IV) infusion of EDB-102. The study will follow a "3+3" design to determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D). Participants will be monitored for adverse events, and tumor biopsies will be collected to assess the gene-editing efficiency of the drug.

Conditions

Non-Small Cell Lung Cancer; Metastatic Non-small Cell Lung Cancer; Liver Metastases; EGFR Gene Mutation; EGFR L858R

Keywords

EDB-102; CRISPR-Cas9; EGFR L858R; Lipid Nanoparticles (LNP); In vivo Gene Editing; TKI Resistance; Osimertinib Resistance

Outcome Measures

Primary Outcomes (2)

• Adverse Events (AEs) and Serious Adverse Events (SAEs)

  AE monitoring throughout the study duration (up to 2 years post-dose).

• Incidence of Dose-Limiting Toxicity (DLT)

  DLT observation period is 28 days after the first dose

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Day 28 after administration, end of follow-up, and at early withdrawal.

• EGFR Protein Expression Level

  Baseline (Pre-dose) and Post-treatment (e.g., Day 21 or Day 28).

• Knockout Efficiency of EGFR-L858R Mutant Gene

  Baseline and Day 28 post-administration

Study Arms (1)

EDB-102

EXPERIMENTAL

Participants will receive a single intravenous infusion of EDB-102. This study follows a dose-escalation design with planned dose cohorts at 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg.

Genetic: EDB-102

Interventions

EDB-102 GENETIC

1. Premedication: To reduce immune and infusion-related reactions to the LNP vector, subjects must receive one of the following before dosing: (i) IV corticosteroid (e.g., dexamethasone 10 mg or equivalent); (ii) H1 antagonist, IV (e.g., diphenhydramine 20 mg) or oral (e.g., cetirizine 10 mg); or (iii) H2 antagonist, IV or oral (e.g., famotidine 20 mg). 2. Intervention: The investigational product will be administered by 2-hour IV infusion. If infusion reactions occur, the infusion may be slowed or extended, but total time from vial opening to completion must not exceed 4 hours. Subjects will be hospitalized for ≥96 hours post-dose; observation may be prolonged if clinically indicated. 3. Frequency: Dose Escalation: Single IV dose on Day 0, followed by a 28-day DLT observation period. Dose Expansion (post-MTD): Q4W dosing for up to 3 cycles, subject to safety data.

EDB-102

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 years, any sex.
• Histologically or cytologically confirmed, unresectable locally advanced or metastatic (stage IV) non-small cell lung cancer (NSCLC)
• Prior treatment with at least one third-generation EGFR-TKI (e.g., osimertinib) with radiologically confirmed disease progression according to RECIST 1.1 or intolerance, and no concomitant anticancer therapy during this period.
• Availability of tumor tissue obtained after progression on third-generation EGFR-TKI, with EGFR L858R mutation confirmed in the post-progression tumor tissue or blood sample by central laboratory- or study site-validated methods (e.g., WES or RNAseq).
• At least one measurable hepatic lesion per RECIST 1.1, confirmed by biopsy, with the EGFR L858R mutation verified in the lesion by central laboratory- or study site-validated methods (e.g., WES or RNAseq).
• ECOG performance status of 0 or 1.
• Adequate organ and bone marrow function: a) Hematologic: within 14 days prior to enrollment and without recent transfusion or growth factor therapy: ANC ≥1.5×10⁹/L, Hb ≥90 g/L, PLT ≥75×10⁹/L, WBC \>3.0×10⁹/L. b) Hepatic: TBIL ≤1.5×ULN, ALT ≤5×ULN, AST ≤5×ULN. c) Renal: serum creatinine ≤1.5×ULN or creatinine clearance (CrCl) ≥50 mL/min. d) Coagulation: PT ≤1.5×ULN, APTT ≤1.5×ULN, INR ≤1.5×ULN.
• Ability and willingness to provide written informed consent, comply with study procedures, and cooperate with study personnel.

You may not qualify if:

• Prior exposure to any gene-editing therapies (e.g., CRISPR, TALEN, ZFN)
• Receipt of chemotherapy, radiotherapy, biologic therapy, endocrine therapy, targeted therapy, immunotherapy, or other anticancer agents within 4 weeks prior to the first dose of study drug. For oral fluoropyrimidines or small-molecule targeted agents, the washout period is 2 weeks or 5 half-lives of the drug, whichever is longer
• Receipt of any investigational, unapproved therapy within 4 weeks prior to the first dose of study drug.
• Presence of other known driver gene alterations conferring TKI resistance, excluding EGFR mutations, unless these occur as co-mutations, including: Bypass pathway activation: High-level MET amplification: detected by WES (gene copy number \>5) or FISH (MET/CEP7 ratio ≥2.0). High-level HER2 amplification: detected by ISH (gene copy number ≥6 per nucleus, HER2/CEP17 ratio ≥2.0). Other acquired resistance driver mutations: Newly emerged confirmed resistance mutations, e.g., KRAS or BRAF-V600E. Activating mutations in PI3K/AKT/mTOR pathway genes (e.g., PIK3CA). Loss of primary EGFR mutation: absence of the original EGFR L858R mutation in post-resistance tumor tissue.
• Known allergy or adverse reaction to any lipid nanoparticle (LNP) components.
• Uncontrolled hypertension (systolic BP \>150 mmHg and/or diastolic BP \>100 mmHg despite regular antihypertensive therapy) or history of hypertensive crisis or hypertensive encephalopathy.
• Liver disease, including cirrhosis, hepatitis, or history of hepatitis B or C infection.
• Unstable angina or acute myocardial infarction, or history of these events within the past 6 months.
• History of malignancy within the past 5 years, except for treated basal cell carcinoma, cutaneous squamous cell carcinoma, cervical cancer, or gastrointestinal cancers.
• Pregnant, breastfeeding, positive pregnancy test, or unwillingness to use contraception in premenopausal women. Women are considered postmenopausal if amenorrheic for ≥2 years. Male patients unwilling to use contraception during the study are also excluded.
• Leptomeningeal, brainstem, or spinal metastases, or active CNS metastases with compression. Subjects with previously treated brain metastases may participate if clinically stable ≥4 weeks prior to first study drug administration and off corticosteroids for ≥14 days.
• Any condition deemed by the investigator to make the subject unsuitable for participation in the study.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ning Li, PhD

  Chinese Academy of Medical Sciences & Peking Union Medical College

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shuhang Wang, PhD

CONTACT

13581809307; wangshuhang@cicams.ac.cn

Aiwen Jian, Bachelor

CONTACT

18259205792; jaw_evin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2026
• First Posted: March 10, 2026
• Study Start: February 10, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 31, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share