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

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05981066
• Other study ID #: J-23PJ957
• Status: Recruiting
• Phase: N/A
• Start date: July 10, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: July 2023
• Source: Peking Union Medical College Hospital
• Contact: Zhao haitao, Dr
• Phone: 010-69156114
• Email: zhaoht[@]pumch.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Neoantigen vaccine, I.M injection
Patients will receive a fixed applicable dose of ABOR2014(IPM511) administered.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Clinically significant abnormal changes in vital signs		up to 12 months
Primary	Clinically significant abnormal changes in laboratory tests		up to 12 months
Secondary	Maximum Plasma Concentration [Cmax] of IPM511		up to 12 months
Secondary	Time of Maximum Plasma Concentration [Tmax] of IPM511		up to 12 months
Secondary	Half-time of Plasma Concentration [T1/2] of IPM511		up to 12 months
Secondary	Antigen-specific T-cell responses in peripheral blood	Detected by Tetramer or TCRseq or Enzyme-linked Immunospot Assay(ELISPOT)	up to 12 months
Secondary	Change of Circulating tumor DNA (ctDNA) status (every 6 weeks)		up to 12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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