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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Neoantigen vaccine, I.M injection

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zhao haitao, Dr; Phone Number: 010-69156114; Email: zhaoht@pumch.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Recruiting
      • Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
      • Contact: tong li, PhD; Email: tong.li@immmupeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 5, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: mRNA vaccine
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: J-23PJ957

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No