Hepatocellular CarcinomaPhase 1NCT07580261
YMN-A02 for Advanced Primary Hepatocellular Carcinoma.
A Phase 1 study testing YMN-A02 100μg, YMN-A02 250μg and YMN-A02 500μg in people with Hepatocellular Carcinoma, run by West China Hospital at 1 site in China.
Trial summary
Primary liver cancer (Hepatocellular carcinoma, HCC) represents a major challenge in clinical oncology and poses a serious threat to public health. In recent years, the application of immune checkpoint inhibitors (ICIs) has transformed the landscape of cancer therapy, demonstrating remarkable efficacy in a subset of… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- YMN-A02 100μg, YMN-A02 250μg and YMN-A02 500μg
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 30 Jul 2026to 30 Jun 2028
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent: Signed informed consent form approved by the ethics committee.
- Age and performance status: Aged 18-70 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
- Patients with histologically confirmed advanced primary hepatocellular carcinoma that has progressed after treatment with anti-angiogenic targeted therapy and immune checkpoint inhibitors.
- At least one target lesion with a measurable diameter according to RECIST criteria (longest diameter of tumor lesion ≥10 mm on CT scan; short diameter of lymph node lesion ≥10 mm on CT scan; slice thickness ≤5 mm).
- Life expectancy: ≥3 months.
- Adequate major organ function, as verified by the following laboratory and test results obtained within 14 days prior to randomization:
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- Hematology: Hemoglobin ≥80 g/L (no blood transfusion within 14 days); absolute neutrophil count >1.5×10⁹/L; platelet count ≥80×10⁹/L.
- Biochemistry: Total bilirubin ≤1.5× upper limit of normal (ULN); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5×ULN; if liver metastases are present, ALT or AST ≤5×ULN; endogenous creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
- Cardiac assessment: Left ventricular ejection fraction (LVEF) ≥50% as assessed by Doppler echocardiography.
- Good compliance and follow-up agreement: The patient is compliant and the family agrees to cooperate with survival follow-up.
Who cannot join
- Participation in another clinical trial of an investigational drug within 4 weeks prior to enrollment.
- Previous or concurrent diagnosis of another malignancy, except for the following: carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, urothelial carcinoma of the bladder that has been treated with curative intent, or any other malignancy that has been treated with curative intent with no evidence of recurrence for 5 years or more.
- Presence of poorly controlled cardiac disease or clinical symptoms, including but not limited to: New York Heart Association (NYHA) Class ≥2 heart failure, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
- Pregnant or breastfeeding women.
- Presence of active infection, including but not limited to: active tuberculosis, bacterial or fungal infection requiring systemic treatment (NCI-CTCAE v5.0 Grade ≥2), human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection (HBV DNA above the upper limit of normal), or active hepatitis C virus (HCV) infection (HCV RNA above the upper limit of normal).
- History of psychotropic substance abuse that cannot be abstained from, or history of mental disorders.
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- Presence of active autoimmune disease or history of autoimmune disease (including but not limited to: uveitis, enteritis, hypophysitis, nephritis, hyperthyroidism, hypothyroidism, etc.). The following are exceptions: vitiligo controlled with topical medication only; childhood asthma that has completely resolved and requires no intervention in adulthood; patients with asthma requiring bronchodilators for medical intervention are not eligible.
- Prior vaccination with any mRNA-based drug or mRNA formulation.
- Prior participation in clinical trials involving lipid nanoparticle (LNP) formulations.
- Contraindications to intravenous infusion.
- History of drug abuse, or medical, psychological, or social conditions (such as history of alcoholism or drug addiction) that, in the investigator's judgment, may affect compliance with the study.
- Known allergy, hypersensitivity, or intolerance to any component of the study formulation (including active ingredients and excipients); history of severe drug, food, or vaccine allergy, including but not limited to: anaphylactic shock, allergic laryngeal edema, allergic dyspnea, anaphylactoid purpura, thrombocytopenic purpura, or Arthus reaction.
- Pregnancy plan (for female subjects or partners of male subjects) from the screening period until 12 months after the last dose.
- Any concomitant disease that, in the investigator's judgment, may jeopardize patient safety or interfere with the completion of the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
West China Hospital
Chengdu, Sichuan, 610041
Peng Xingchen Professor, 18980606753, pxx2014@scu.edu.cn
About this study
Official title: A Phase I Clinical Study of YMN-A02, a Bifunctional RNA Agent, for Safety, Tolerability, and Preliminary Efficacy in Patients With Advanced Primary Liver Cancer Who Have Failed Standard of Care
Primary liver cancer (Hepatocellular carcinoma, HCC) represents a major challenge in clinical oncology and poses a serious threat to public health. In recent years, the application of immune checkpoint inhibitors (ICIs) has transformed the landscape of cancer therapy, demonstrating remarkable efficacy in a subset of patients. However, due to the unique immune-tolerant microenvironment of the liver, tumor cells can evade host immune surveillance, leading to reduced immune cell infiltration and T cell exhaustion. Consequently, patients with advanced HCC often respond poorly to existing ICI therapies. Transforming growth factor-beta (TGF-β), a key regulator of T cell immune responses, is highly expressed in the tumor microenvironment and mediates immune evasion by inducing regulatory T cell (Treg) differentiation and suppressing the effector functions of CD8⁺ T cells. Therefore, simultaneous blockade of immune checkpoints and the TGF-β signaling pathway represents a promising strategy to reverse immune tolerance in liver tumors.
Based on the above mechanisms, our research team has developed an RNA formulation (YMN-A02 bifunctional RNA formulation) encapsulated in TM10-LNP, which encodes a bifunctional fusion protein combining a CTLA-4 antibody and a TGF-β trap. Preclinical studies have shown that this formulation effectively activates antitumor immune responses and inhibits tumor growth in orthotopic liver cancer animal models. This study proposes a Phase I clinical trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of this formulation in patients with advanced primary liver cancer who have failed standard treatment, aiming to provide a new strategy for overcoming immune tolerance in liver tumors and improving the response rate to immunotherapy.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- YMN-A02 100μg, YMN-A02 250μg, YMN-A02 500μg, YMN-A02 1000μg
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YMN-A02 100μgBiological
Enrolled subjects will receive a 100 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion.
YMN-A02 250μgBiological
Enrolled subjects will receive a 250 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion.
YMN-A02 500μgBiological
Enrolled subjects will receive a 500 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion.
YMN-A02 1000μgBiological
Enrolled subjects will receive a 1000 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion.
| Study group | Role | What they receive |
|---|---|---|
| YMN-A02 100 μg Group | Experimental | Enrolled subjects will receive a 100 μg intravenous infusion. Receives: Biological: YMN-A02 100μg |
| YMN-A02 250 μg Group | Experimental | Enrolled subjects will receive a 250 μg intravenous infusion. Receives: Biological: YMN-A02 250μg |
| YMN-A02 500 μg Group | Experimental | Enrolled subjects will receive a 500 μg intravenous infusion. Receives: Biological: YMN-A02 500μg |
| YMN-A02 1000 μg Group | Experimental | Enrolled subjects will receive a 1000 μg intravenous infusion. Receives: Biological: YMN-A02 1000μg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Dose-Limiting Toxicity (DLT)
Observe and record the occurrence of DLTs. DLT is defined as treatment-related adverse events or clinically significant laboratory abnormalities occurring during the DLT observation period, graded according to NCI CTCAE v5.0.
Measured: From first dose to 14 days after the third dose, approximately Day 0 to Day 42
Secondary outcomes (2)
Progression-Free Survival (PFS)
Assess disease progression per RECIST v1.1, calculating the time from start of treatment to first documented disease progression or death from any cause.
Measured: Within 2 years after the first dose
Objective Response Rate (ORR)
Tumor response assessed per RECIST v1.1 for solid tumors. ORR is the proportion of patients whose tumor volume reduction reaches a predefined value and is maintained for a minimum required duration, calculated as the sum of complete response (CR) and partial response (PR) rates.
Measured: Within 6 months after the first dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2026
- Study start30 Jul 2026 (estimated)
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by West China HospitalThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xingchen Peng, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07580261
- Sponsor's protocol ID
- 2026(889)
- Status last verified
- Apr 2026
- First submitted
- 26 Apr 2026
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Study of YMN-A02, a Bifunctional RNA Agent, for Safety, Tolerability, and Preliminary Efficacy in Patients With Advanced Primary Liver Cancer Who Have Failed Standard of Care
- ClinicalTrials.gov ID
- NCT07580261
- Acronym / sponsor ID
- 2026(889)
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 30 Jul 2026 (estimated)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 12 May 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.
Primary liver cancer (Hepatocellular carcinoma, HCC) represents a major challenge in clinical oncology and poses a serious threat to public health. In recent years, the application of immune checkpoint inhibitors (ICIs) has transformed the landscape of cancer therapy, demonstrating remarkable efficacy in a subset of patients. However, due to the unique immune-tolerant microenvironment of the liver, tumor cells can evade host immune surveillance, leading to reduced immune cell infiltration and T cell exhaustion. Consequently, patients with advanced HCC often respond poorly to existing ICI therapies. Transforming growth factor-beta (TGF-β), a key regulator of T cell immune responses, is highly expressed in the tumor microenvironment and mediates immune evasion by inducing regulatory T cell (Treg) differentiation and suppressing the effector functions of CD8⁺ T cells. Therefore, simultaneous blockade of immune checkpoints and the TGF-β signaling pathway represents a promising strategy to reverse immune tolerance in liver tumors.
Based on the above mechanisms, our research team has developed an RNA formulation (YMN-A02 bifunctional RNA formulation) encapsulated in TM10-LNP, which encodes a bifunctional fusion protein combining a CTLA-4 antibody and a TGF-β trap. Preclinical studies have shown that this formulation effectively activates antitumor immune responses and inhibits tumor growth in orthotopic liver cancer animal models. This study proposes a Phase I clinical trial to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of this formulation in patients with advanced primary liver cancer who have failed standard treatment, aiming to provide a new strategy for overcoming immune tolerance in liver tumors and improving the response rate to immunotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| YMN-A02 100 μg Group | Experimental | Biological: YMN-A02 100μgEnrolled subjects will receive a 100 μg intravenous infusion. |
| YMN-A02 250 μg Group | Experimental | Biological: YMN-A02 250μgEnrolled subjects will receive a 250 μg intravenous infusion. |
| YMN-A02 500 μg Group | Experimental | Biological: YMN-A02 500μgEnrolled subjects will receive a 500 μg intravenous infusion. |
| YMN-A02 1000 μg Group | Experimental | Biological: YMN-A02 1000μgEnrolled subjects will receive a 1000 μg intravenous infusion. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Informed consent: Signed informed consent form approved by the ethics committee.
- Age and performance status: Aged 18-70 years; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
- Patients with histologically confirmed advanced primary hepatocellular carcinoma that has progressed after treatment with anti-angiogenic targeted therapy and immune checkpoint inhibitors.
- At least one target lesion with a measurable diameter according to RECIST criteria (longest diameter of tumor lesion ≥10 mm on CT scan; short diameter of lymph node lesion ≥10 mm on CT scan; slice thickness ≤5 mm).
- Life expectancy: ≥3 months.
Key exclusion criteria (14 listed)
- Participation in another clinical trial of an investigational drug within 4 weeks prior to enrollment.
- Previous or concurrent diagnosis of another malignancy, except for the following: carcinoma in situ of the cervix, cutaneous squamous cell carcinoma, urothelial carcinoma of the bladder that has been treated with curative intent, or any other malignancy that has been treated with curative intent with no evidence of recurrence for 5 years or more.
- Presence of poorly controlled cardiac disease or clinical symptoms, including but not limited to: New York Heart Association (NYHA) Class ≥2 heart failure, unstable angina, myocardial infarction within the past year, or clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
- Pregnant or breastfeeding women.
- Presence of active infection, including but not limited to: active tuberculosis, bacterial or fungal infection requiring systemic treatment (NCI-CTCAE v5.0 Grade ≥2), human immunodeficiency virus (HIV) infection, active hepatitis B virus (HBV) infection (HBV DNA above the upper limit of normal), or active hepatitis C virus (HCV) infection (HCV RNA above the upper limit of normal).
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 |
|---|---|---|
| YMN-A02 100μgEnrolled subjects will receive a 100 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion. | Biological | YMN-A02 100 μg Group |
| YMN-A02 250μgEnrolled subjects will receive a 250 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion. | Biological | YMN-A02 250 μg Group |
| YMN-A02 500μgEnrolled subjects will receive a 500 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion. | Biological | YMN-A02 500 μg Group |
| YMN-A02 1000μgEnrolled subjects will receive a 1000 μg intravenous infusion according to their assigned dose group. The dosing regimen includes 5 doses of primary immunization followed by subsequent individualized treatment. The first 4 doses of primary immunization are administered once weekly (Q1W), and the 5th dose is administered one month after the 4th dose. The DLT observation period is from the first infusion to 14 days after the third infusion. | Biological | YMN-A02 1000 μg Group |
Primary outcome
Occurrence of Dose-Limiting Toxicity (DLT)
Time frame: From first dose to 14 days after the third dose, approximately Day 0 to Day 42
Observe and record the occurrence of DLTs. DLT is defined as treatment-related adverse events or clinically significant laboratory abnormalities occurring during the DLT observation period, graded according to NCI CTCAE v5.0.
2 secondary outcomes
Progression-Free Survival (PFS)
Time frame: Within 2 years after the first dose
Objective Response Rate (ORR)
Time frame: Within 6 months after the first dose
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 12 May 2026.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing YMN-A02 100μg, YMN-A02 250μg and YMN-A02 500μg in people with Hepatocellular Carcinoma, run by West China Hospital at 1 site in China.
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 10 inclusion and 14 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 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Peng Xingchen Peng (86-017723609529, pxx2014@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of Dose-Limiting Toxicity (DLT) (time frame: From first dose to 14 days after the third dose, approximately Day 0 to Day 42). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 May 2026.