YMN-A02 for Advanced Primary Hepatocellular Carcinoma.

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 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

Interventions

BIOLOGICAL

YMN-A02 100μg

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.

BIOLOGICAL

YMN-A02 250μg

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.

BIOLOGICAL

YMN-A02 500μg

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.

BIOLOGICAL

YMN-A02 1000μg

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.

Sponsors & Collaborators

• West China Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-30

Primary Completion

2028-06-30

Completion

2028-06-30

Countries

• China

Study Locations