Phase I/II Multicenter Trial of a Novel Therapeutic Cancer Vaccine, HepaVac-101, for Hepatocellular Carcinoma

Author:

Löffler Markus W.12345ORCID,Gori Stefania6,Izzo Francesco7ORCID,Mayer-Mokler Andrea8,Ascierto Paolo A.9ORCID,Königsrainer Alfred134ORCID,Ma Yuk Ting10,Sangro Bruno11ORCID,Francque Sven12,Vonghia Luisa12ORCID,Inno Alessandro6ORCID,Avallone Antonio13,Ludwig Jörg8,Alcoba Diego Duarte8,Flohr Christian8,Aslan Katrin8,Mendrzyk Regina8,Schuster Heiko8,Borrelli Marco13ORCID,Valmori Danila14,Chaumette Tanguy14ORCID,Heidenreich Regina15,Gouttefangeas Cécile23,Forlani Greta16ORCID,Tagliamonte Maria17ORCID,Fusco Caterina18ORCID,Penta Roberta18,Iñarrairaegui Mercedes11,Gnad-Vogt Ulrike15,Reinhardt Carsten8,Weinschenk Toni8ORCID,Accolla Roberto S.16ORCID,Singh-Jasuja Harpreet8,Rammensee Hans-Georg234ORCID,Buonaguro Luigi17ORCID

Affiliation:

1. 1Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, Tübingen, Germany.

2. 2Interfaculty Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.

3. 3Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, Tübingen, Germany.

4. 4German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Tübingen, Germany.

5. 5Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.

6. 6Medical Oncology, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar di Valpolicella (Verona), Italy.

7. 7Hepatobiliary Surgery Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples, Italy.

8. 8Immatics Biotechnologies GmbH, Tübingen, Germany.

9. 9Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples, Italy.

10. 10Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.

11. 11Liver Unit, Clinica Universidad de Navarra and CIBEREHD, Pamplona, Spain.

12. 12Division of Gastroenterology and Hepatology, Antwerp University Hospital, Edegem, Belgium.

13. 13Experimental Clinical Abdominal Oncology Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples, Italy.

14. 14EA3826 Thérapeutiques Anti-Infectieuses, Institut de Recherche en Santé 2 Nantes Biotech, Université de Nantes, Nantes, France.

15. 15CureVac AG, Tübingen, Germany.

16. 16Department of Medicine and Surgery, University of Insubria, Varese, Italy.

17. 17Innovative Immunological Models Unit, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale, Naples, Italy.

18. 18Ba.S.C.O. Unit, Cellular Manipulation and Immunogenetics, Oncology Department, AORN Santobono-Pausilipon, Naples, Italy.

Abstract

Abstract Purpose: Immunotherapy for hepatocellular carcinoma (HCC) shows considerable promise in improving clinical outcomes. HepaVac-101 represents a single-arm, first-in-human phase I/II multicenter cancer vaccine trial for HCC (NCT03203005). It combines multipeptide antigens (IMA970A) with the TLR7/8/RIG I agonist CV8102. IMA970A includes 5 HLA-A*24 and 7 HLA-A*02 as well as 4 HLA-DR restricted peptides selected after mass spectrometric identification in human HCC tissues or cell lines. CV8102 is an RNA-based immunostimulator inducing a balanced Th1/Th2 immune response. Patients and Methods: A total of 82 patients with very early- to intermediate-stage HCCs were enrolled and screened for suitable HLA haplotypes and 22 put on study treatment. This consisted in a single infusion of low-dose cyclophosphamide followed by nine intradermal coadministrations of IMA970A and CV8102. Only patients with no disease relapse after standard-of-care treatments were vaccinated. The primary endpoints of the HepaVac-101 clinical trial were safety, tolerability, and antigen-specific T-cell responses. Secondary or exploratory endpoints included additional immunologic parameters and survival endpoints. Results: The vaccination showed a good safety profile. Transient mild-to-moderate injection-site reactions were the most frequent IMA970A/CV8102-related side effects. Immune responses against ≥1 vaccinated HLA class I tumor-associated peptide (TAA) and ≥1 vaccinated HLA class II TAA were respectively induced in 37% and 53% of the vaccinees. Conclusions: Immunotherapy may provide a great improvement in treatment options for HCC. HepaVac-101 is a first-in-human clinical vaccine trial with multiple novel HLA class I– and class II–restricted TAAs against HCC. The results are initial evidence for the safety and immunogenicity of the vaccine. Further clinical evaluations are warranted.

Funder

FP-7 HEPAVAC

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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