SARS-CoV-2 mRNA Vaccination in Patients With Hepatocellular Carcinoma Treated With Immune Checkpoint Inhibitors (CoVaCheck)

SARS-CoV-2 mRNA Vaccination in Patients With Hepatocellular Carcinoma Treated With Immune Checkpoint Inhibitors (CoVaCheck) A Multicenter Retrospective Cohort Analysis in Austria

A multicenter retrospective cohort analysis in Austria

Primary Objective:

To assess whether receiving an mRNA COVID-19 vaccine within 3 months before starting ICI (Immune checkpoint inhibitors) therapy improves best overall response (mRECIST) in HCC (hepatocellular carcinoma).

Secondary Objectives:

Evaluate whether vaccination within 1 or 3 months affects OS (overall survival) , PFS (Progression free survival)), or TTP (Time to progression); compare outcomes by vaccination status, vaccine type, and prior infection; explore modification by cirrhosis severity and tumor characteristics; and assess safety (irAEs, steroid use, toxicity-related discontinuation).

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma; Checkpoint Inhibitor; mRNA Vaccination

Detailed Description

Immune checkpoint inhibitors (ICIs) have become a cornerstone of systemic therapy for advanced hepatocellular carcinoma (HCC). Their efficacy, however, varies substantially between patients, and factors that modulate immunotherapy response remain incompletely understood .

Recent mechanistic and clinical data have raised the hypothesis that SARS-CoV-2 mRNA vaccines might augment responsiveness to ICIs. A landmark study by Grippin et al. demonstrated that mRNA vaccines induce a systemic surge of type-I interferons, activate antigen-presenting cells, increase PD-L1 expression on tumor cells, and ultimately sensitize tumors to ICIs across various malignancies including NSCLC (non-small cell lung cancer) and melanoma. In their retrospective cohorts, receiving a COVID-19 mRNA vaccine within 100 days before starting ICI was associated with significantly improved overall survival and progression-free survival While these findings suggest that COVID-19 mRNA vaccines may act as potent immune modulators in the context of immunotherapy, no data exist for HCC, a tumor entity that is characterized by an immunosuppressive, 'immune-cold' microenvironment that limits effective anti-tumor immune responses.

Given the widespread implementation of COVID-19 vaccination programs in Austria since 2021, and the large number of HCC patients receiving ICI-based therapies at tertiary centers, a rigorous retrospective analysis is now feasible.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Florian Rainer, MD; Phone Number: 30164 +43 316 385; Email: florian.rainer@medunigraz.at
• Study Contact Backup: Name: Vanessa Stadlbauer, Univ. Prof. MD; Phone Number: 82282 +43 316 385; Email: vanessa.stadlbauer@medunigraz.at

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medical University of Graz
    • Contact: Florian Rainer, MD; Phone Number: +43 316 385; Email: florian.rainer@medunigraz.at
  • Linz, Austria
    • Ordensklinikum Linz
    • Contact: Stephanie Hametner-Schreil; Phone Number: +43 732 7677; Email: Stephanie.Hametner-Schreil@ordensklinikum.at
  • Sankt Pölten, Austria
    • University hospital St. Pölten
    • Contact: Anderas Maieron, MD; Phone Number: +43 27429004; Email: andreas.maieron@stpoelten.lknoe.at
  • Sankt Veit an der Glan, Austria
    • Krankenhaus der Barmherzigen Brüder St Veit an der Glan
    • Contact: Ute Enökl-Tomantschger, MD; Phone Number: +43 4212 499; Email: Ute.Enoekl-Tomantschger@bbstveit.at
  • Wels, Austria
    • Klinikum Wels-Grieskirchen
    • Contact: Harald Hofer, MD; Phone Number: +43 7242 415 - 2181; Email: harald.hofer@klinikum-wegr.at

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The study will include all eligible patients with HCC treated within the past 5 years (January 2021 - December 2025, depending on center availability) with one of the specified checkpoint inhibitors

Description

Inclusion Criteria:

• Age ≥ 18 years
• Radiologically or histologically confirmed hepatocellular carcinoma
• Treatment with immune checkpoint inhibitor-based therapy (mono- or combination therapy; e.g., atezolizumab/bevacizumab, durvalumab/tremelimumab, nivolumab, pembrolizumab)
• Complete electronic medical records available
• At least one imaging-based response assessment using mRECIST

Exclusion Criteria:

• Missing key clinical data required for main analyses (e.g. survival status, date of progression, Child-Pugh class, BCLC stage)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Vaccinated; Patients with hepatocellular carcinoma, undergoing checkpoint inhibitor therapy, vaccinated with mRNA vaccine within last 100 days
not vaccinated; Patients with hepatocellular carcinoma, undergoing checkpoint inhibitor therapy, not vaccinated with mRNA vaccine within last 100 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best overall response	according to mRECIST criteria	up to 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	death yes/no	up to 4 years
Progression free survival	Progression according to RECIST yes/no	up to 4 years
Time to progression	Time until progression occurs according to RECIST	up to 4 years

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Klinikum Wels-Grieskirchen; Krankenhaus der Barmherzigen Brüder St. Veit/Glan; University Hospital St. Polten; Ordensklinikum Linz GmbH Krankenhaus Barmherzige Schwestern
• Investigators: Principal Investigator: Florian Rainer, MD, Medizinische Universitat Graz; Principal Investigator: Vanessa Stadlbauer, Univ Prof, Medizinische Universitat Graz; Principal Investigator: Walter Spindelböck, MD, Medizinische Universitat Graz

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: January 7, 2026
• First Posted (Actual): January 14, 2026

Study Record Updates

• Last Update Posted (Actual): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 7, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: response; hepatocellular carcinoma; mRNA vaccination; immune checkpoint inhibitor
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: CoVaCheck

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request and after having a data sharing agreement in place, pseudonymized IPD can be shared.

Drug and device information, study documents

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