Advanced Hepatocellular Carcinoma
Conditions
Keywords
mRNA vaccine
Brief summary
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.
Interventions
DRUGNeoantigen vaccine, I.M injection
Patients will receive a fixed applicable dose of ABOR2014(IPM511) administered.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects who understand and voluntarily sign the informed consent form; 2. Male or female subjects ≥ 18 years old; 3. Patients with pathological or cytological evidence of locally advanced or hepatocellular carcinoma, who have failed or are intolerant of previous standard treatments; 4. At least one measurable lesion judged according to the RECIST version 1.1 standard. 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (inclusive); 6. Life expectancy ≥ 12 weeks; 7. HLA typing: A-02; 8. 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; 9. 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
1. Known allergy to any of the components of the investigational product; 2. History of topical treatment with mRNA products or treatment with mRNA vaccines; 3. 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); 4. History of anti-tumor therapies within 4 weeks before the first dose; 5. 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; 6. History of organ transplant, bone marrow transplant, or hematopoietic stem cell transplant; 7. History of hemorrhagic diseases such as anaphylactoid purpura, Haemophilia and aplastic anemia; 8. History of live attenuated vaccines within 30 days before the first dose; 9. Central nervous system (CNS) metastases that are symptomatic, untreated, or require continuous treatment; 10. Toxicological events (except alopecia and pigmentation) have not recovered to baseline or NCI-CTCAE v5.0 grade 0-1 after prior anti-tumor therapies; 11. History of autoimmune disorders; 12. History of immediate hypersensitivity, eczema that cannot be controlled by topical corticosteroids, or asthma; 13. Uncontrollable concomitant diseases; 14. Active infections currently requiring systemic anti-infective therapy; active pulmonary tuberculosis; 15. Known history of human immunodeficiency virus (HIV) positive or treponema pallidum positive; 16. Patients with other conditions that are not suitable for participation in the study at the discretion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events (AE) | up to 12 months | AE assessed according to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). |
| Clinically significant abnormal changes in vital signs | up to 12 months | — |
| Clinically significant abnormal changes in laboratory tests | up to 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response, DoR | up to 12 months | 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). |
| Progress Free Survival, PFS | up to 12 months | 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). |
| Overall Survival, OS | up to 12 months | OS is defined as time between the date of first dose of IPM511 and the date of death due to any cause. |
| Antigen-specific T-cell responses in peripheral blood | up to 12 months | Detected by Tetramer or TCRseq or Enzyme-linked Immunospot Assay(ELISPOT) |
| 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 | — |
| Maximum Plasma Concentration [Cmax] of IPM511 | up to 12 months | — |
| Change of Circulating tumor DNA (ctDNA) status (every 6 weeks) | up to 12 months | — |
| Objective Response Rate, ORR | up to 12 months | ORR is Defined as the number of patients with a complete response (CR) or partial response(PR) . |
Countries
China
Contacts
Primary ContactZhao haitao, Dr
Outcome results
None listed