Non-Small Cell Lung CancerPhase 1NCT07461727

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

A Phase 1 study testing EDB-102 in people with Non-Small Cell Lung Cancer and Metastatic Non-small Cell Lung Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Non-Small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer, Liver Metastases
What is being tested?: EDB-102
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 15 participants
Where: No sites listed yet
Study dates: 10 Feb 2026to 31 Jan 2029
Phase: Phase 1
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Shuhang Wang, PhD contact

13581809307

wangshuhang@cicams.ac.cn

Aiwen Jian, Bachelor contact

18259205792

jaw_evin@163.com

About this study

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.

Read the 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.

Conditions: Non-Small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer, Liver Metastases, EGFR Gene Mutation, EGFR L858R
Being tested: EDB-102
Keywords: EDB-102, CRISPR-Cas9, EGFR L858R, Lipid Nanoparticles (LNP), In vivo Gene Editing, TKI Resistance, Osimertinib Resistance
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EDB-102Genetic
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.

Study groups in NCT07461727
Study group	Role	What they receive
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. Receives: Genetic: EDB-102

What is being measured

The primary outcome is the main question the study is designed to answer.

Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: AE monitoring throughout the study duration (up to 2 years post-dose).
Incidence of Dose-Limiting Toxicity (DLT)
Measured: DLT observation period is 28 days after the first dose

Secondary outcomes (3)

Objective Response Rate (ORR)
Measured: Day 28 after administration, end of follow-up, and at early withdrawal.
EGFR Protein Expression Level
Measured: Baseline (Pre-dose) and Post-treatment (e.g., Day 21 or Day 28).
Knockout Efficiency of EGFR-L858R Mutant Gene
Measured: Baseline and Day 28 post-administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Feb 202631 Jan 2029

First posted10 Mar 2026
Study start10 Feb 2026 (estimated)
Primary completion1 Jan 2027 (estimated)
Study completion31 Jan 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 15 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07461727
Sponsor's protocol ID: NCC6018/NCCH6018
Status last verified: Feb 2026
First submitted: 5 Mar 2026
Last updated: 10 Mar 2026
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT07461727
Acronym / sponsor ID: NCC6018/NCCH6018
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
Phase: Phase 1
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 15 participants (estimated)
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
Study start: 10 Feb 2026 (estimated)
Primary completion: 1 Jan 2027 (estimated)
Study completion: 31 Jan 2029 (estimated)
First posted: 10 Mar 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study Drug and Mechanism:

Study Design:

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.

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:

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.

Immunogenicity: Measurement of anti-Cas9 and anti-LNP antibodies.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
EDB-102	Experimental	Genetic: EDB-102Participants 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.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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).

Key exclusion criteria (12 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EDB-1021. 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.	Genetic	EDB-102

Primary outcome

Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: AE monitoring throughout the study duration (up to 2 years post-dose).
Incidence of Dose-Limiting Toxicity (DLT)
Time frame: DLT observation period is 28 days after the first dose

3 secondary outcomes

Objective Response Rate (ORR)
Time frame: Day 28 after administration, end of follow-up, and at early withdrawal.
EGFR Protein Expression Level
Time frame: Baseline (Pre-dose) and Post-treatment (e.g., Day 21 or Day 28).
Knockout Efficiency of EGFR-L858R Mutant Gene
Time frame: Baseline and Day 28 post-administration

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Shuhang Wang, PhD contact

13581809307

wangshuhang@cicams.ac.cn

Aiwen Jian, Bachelor contact

18259205792

jaw_evin@163.com

Ning Li, PhD principal investigator

Chinese Academy of Medical Sciences & Peking Union Medical College

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing EDB-102 in people with Non-Small Cell Lung Cancer and Metastatic Non-small Cell Lung Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Shuhang Wang, PhD (13581809307, wangshuhang@cicams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: AE monitoring throughout the study duration (up to 2 years post-dose).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07461727.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.