A Clinical Study of mRNA Vaccine (ABOR2014/IPM511) in Patients With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is an open label, single-site, investigator-initiated trial designed to evaluate the safety, tolerability and preliminary efficacy of ABOR2014(IPM511) injection in relapsed/ refactory HCC.

Official Title
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An Open, Single-center, Multiple-dose, Dose-increasing and Dose-expanding Clinical Study to Observe and Evaluate the Safety, Tolerance, Immunokinetics and Preliminary Effectiveness of ABOR2014 Injection (IPM511) in the Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Neoantigen vaccine, I.M injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who understand and voluntarily sign the informed consent form; Male or female subjects ≥ 18 years old; Patients with pathological or cytological evidence of locally advanced or hepatocellular carcinoma, who have failed or are intolerant of previous standard treatments; At least one measurable lesion judged according to the RECIST version 1.1 standard. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (inclusive); Life expectancy ≥ 12 weeks; HLA typing: A-02; Laboratory tests at screening shall meet the following requirements: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelet count (PLT) ≥ 90 × 10^9/L; Hemoglobin (Hb) ≥ 90 g/L; Total bilirubin (TBIL) ≤ 3 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN; Blood creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (calculated based on Cockcroft-Gault formula) ≥ 45 mL/min; International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN; QTc interval (calculated based on Fridericia's formula) ≤ 450 ms for males and ≤ 470 ms for females; For subjects with hepatitis B-related primary hepatocellular carcinoma (HBV-HCC) or hepatitis C-related primary hepatocellular carcinoma (HCV-HCC), those who are with the following conditions are eligible to be enrolled: HBV-HCC: resolved HBV infection with concomitant antiviral therapy; HCV-HCC: resolved or active HCV infection , where concomitant antiviral therapy may be given for active HCV infection; 9. For patients of childbearing potential (male or female), effective contraceptive measures shall be taken during the study treatment and within 3 months after the last dose. For women of childbearing potential, a negative serum/urine HCG test result within 7 days prior to study enrollment shall be provided. Exclusion Criteria: Known allergy to any of the components of the investigational product; History of topical treatment with mRNA products or treatment with mRNA vaccines; Patients with a history of major operations within 4 weeks before the first dose, have a plan of major operations during the study (at the investigator's discretion); History of anti-tumor therapies within 4 weeks before the first dose; History of receiving immunosuppressive drugs within 4 weeks before the first dose, except for corticosteroid nasal sprays, inhalants, and systemic prednisone at a dose of ≤ 10 mg/day or similar drugs at equivalent doses; History of organ transplant, bone marrow transplant, or hematopoietic stem cell transplant; History of hemorrhagic diseases such as anaphylactoid purpura, Haemophilia and aplastic anemia; History of live attenuated vaccines within 30 days before the first dose; Central nervous system (CNS) metastases that are symptomatic, untreated, or require continuous treatment; Toxicological events (except alopecia and pigmentation) have not recovered to baseline or NCI-CTCAE v5.0 grade 0-1 after prior anti-tumor therapies; History of autoimmune disorders; History of immediate hypersensitivity, eczema that cannot be controlled by topical corticosteroids, or asthma; Uncontrollable concomitant diseases; Active infections currently requiring systemic anti-infective therapy; active pulmonary tuberculosis; Known history of human immunodeficiency virus (HIV) positive or treponema pallidum positive; Patients with other conditions that are not suitable for participation in the study at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPM511 monotherapy<br>3+3 dose excalation. Paticipants will receive two cycle (QWX4 per cycle) IPM511 injection，I.M injection | Drug: Neoantigen vaccine, I.M injection<br>* Patients will receive a fixed applicable dose of ABOR2014(IPM511) administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events (AE) | AE assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). | up to 12 months | 
| Clinically significant abnormal changes in vital signs |  | up to 12 months | 
| Clinically significant abnormal changes in laboratory tests |  | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration [Cmax] of IPM511 |  | up to 12 months | 
| Time of Maximum Plasma Concentration [Tmax] of IPM511 |  | up to 12 months | 
| Half-time of Plasma Concentration [T1/2] of IPM511 |  | up to 12 months | 
| Antigen-specific T-cell responses in peripheral blood | Detected by Tetramer or TCRseq or Enzyme-linked Immunospot Assay(ELISPOT) | up to 12 months | 
| Change of Circulating tumor DNA (ctDNA) status (every 6 weeks) |  | up to 12 months | 
| Objective Response Rate, ORR | ORR is Defined as the number of patients with a complete response (CR) or partial response(PR) . | up to 12 months | 
| Duration of Response, DoR | DoR is defined as time from first tumor response(partial or complete) until either radiogical disease progress, clinical/ symptomatic disease progression or death (whichever is sooner). | up to 12 months | 
| Progress Free Survival, PFS | PFS is defined as time between the date of first dose of IPM511 and the date either radiogical disease progress, clinical/ symptomatic disease progression or death (whichever is sooner). | up to 12 months | 
| Overall Survival, OS | OS is defined as time between the date of first dose of IPM511 and the date of death due to any cause. | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA vaccine