Ignite Creation Date:
2026-03-26 @ 3:20 PM
Ignite Modification Date:
2026-03-31 @ 2:47 PM
Study NCT ID:
NCT07461727
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-03-10
First Post:
2026-03-05
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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
Sponsor:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Organization:
Study Overview
Official Title:
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
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
Detailed Description:
This is a single-center, open-label, single-arm, dose-escalation Phase I clinical study designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary anti-tumor activity of EDB-102 Injection in patients with EGFR-L858R mutation-positive advanced NSCLC and liver metastases who have progressed on or are intolerant to third-generation EGFR-TKIs.
Study Drug and Mechanism:
EDB-102 utilizes the CRISPR-Cas9 gene-editing system delivered via lipid nanoparticles (LNPs). The sgRNA is designed to target the NGG PAM sequence generated specifically by the T\>G mutation at the EGFR L858R locus, ensuring high specificity for the mutant allele while sparing the wild-type EGFR. The LNP carrier facilitates delivery primarily to the liver, leveraging the ApoE-mediated endogenous targeting mechanism.
Study Design:
The study consists of a Dose Escalation Phase and a potential Expansion Phase. Dose Escalation: A modified "3+3" design will be used combined with an initial accelerated titration for the lowest dose. Three dose levels are planned: 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg.
Accelerated Titration: For the low-dose cohort (0.1 mg/kg), single-patient cohorts may be used initially. If safety signals (≥ Grade 2 AE) occur, the design switches to standard 3+3.
Standard 3+3: For intermediate and high doses (0.3 mg/kg and above), cohorts will enroll 3 to 6 patients. Dose escalation proceeds based on the incidence of Dose-Limiting Toxicities (DLTs) observed during the 28-day DLT observation period.
Expansion Phase: Once the Maximum Tolerated Dose (MTD) is identified, an expansion cohort may be enrolled at the MTD level to further evaluate safety and PK/PD.
Intervention:
Eligible patients will receive a mandatory premedication regimen (corticosteroids, H1/H2 receptor antagonists) to mitigate infusion-related reactions. EDB-102 is administered as a single intravenous infusion over 2 hours. In the expansion phase, a multi-dose regimen (e.g., Q4W) may be explored based on safety data.
Key Assessments:
Safety: Monitoring of Adverse Events (AEs), SAEs, and DLTs according to CTCAE v5.0. Special attention is paid to infusion-related reactions (IRR), cytokine release syndrome (CRS), and liver toxicity.
Efficacy: Tumor response assessment using RECIST 1.1 at Day 21, Week 24, and subsequent visits.
Pharmacodynamics: Pre- and post-treatment liver tumor biopsies will be collected to quantify gene knockout efficiency (Indel frequency) via Next-Generation Sequencing (NGS) and to assess EGFR protein reduction via IHC. Off-target effects will be monitored using high-depth sequencing.
Immunogenicity: Measurement of anti-Cas9 and anti-LNP antibodies.
Study Drug and Mechanism:
EDB-102 utilizes the CRISPR-Cas9 gene-editing system delivered via lipid nanoparticles (LNPs). The sgRNA is designed to target the NGG PAM sequence generated specifically by the T\>G mutation at the EGFR L858R locus, ensuring high specificity for the mutant allele while sparing the wild-type EGFR. The LNP carrier facilitates delivery primarily to the liver, leveraging the ApoE-mediated endogenous targeting mechanism.
Study Design:
The study consists of a Dose Escalation Phase and a potential Expansion Phase. Dose Escalation: A modified "3+3" design will be used combined with an initial accelerated titration for the lowest dose. Three dose levels are planned: 0.1 mg/kg, 0.3 mg/kg, and 0.6 mg/kg.
Accelerated Titration: For the low-dose cohort (0.1 mg/kg), single-patient cohorts may be used initially. If safety signals (≥ Grade 2 AE) occur, the design switches to standard 3+3.
Standard 3+3: For intermediate and high doses (0.3 mg/kg and above), cohorts will enroll 3 to 6 patients. Dose escalation proceeds based on the incidence of Dose-Limiting Toxicities (DLTs) observed during the 28-day DLT observation period.
Expansion Phase: Once the Maximum Tolerated Dose (MTD) is identified, an expansion cohort may be enrolled at the MTD level to further evaluate safety and PK/PD.
Intervention:
Eligible patients will receive a mandatory premedication regimen (corticosteroids, H1/H2 receptor antagonists) to mitigate infusion-related reactions. EDB-102 is administered as a single intravenous infusion over 2 hours. In the expansion phase, a multi-dose regimen (e.g., Q4W) may be explored based on safety data.
Key Assessments:
Safety: Monitoring of Adverse Events (AEs), SAEs, and DLTs according to CTCAE v5.0. Special attention is paid to infusion-related reactions (IRR), cytokine release syndrome (CRS), and liver toxicity.
Efficacy: Tumor response assessment using RECIST 1.1 at Day 21, Week 24, and subsequent visits.
Pharmacodynamics: Pre- and post-treatment liver tumor biopsies will be collected to quantify gene knockout efficiency (Indel frequency) via Next-Generation Sequencing (NGS) and to assess EGFR protein reduction via IHC. Off-target effects will be monitored using high-depth sequencing.
Immunogenicity: Measurement of anti-Cas9 and anti-LNP antibodies.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: