Effects of Neoadjuvant Immunotherapy on Anti-tumour Immunity in Hepatocellular Carcinoma Patients Undergoing Liver Resection

NCT07461675 | Not Yet Recruiting Phase 3

• 1 other identifier: HCCsurgICI2025
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Our study aims to evaluate the benefit of the administration of immunotherapy (atezolizumab), in patients with hepatocellular carcinoma (HCC), prior surgical resection of the tumor. HCC is the most prevalent primary liver cancer, responsible for nearly 800,000 deaths annually, making it the third leading cause of cancer-related mortality worldwide. Ablation by radiologic micro-waves or surgical resection represent at the moment the only curative therapies for early stages of the disease. Despite these curative options, HCC recurrence is frequent. Recently, immunotherapy has demonstrated good results on patient overall survival for advanced stages of HCC in comparison to sorafenib. Because of the beneficial effect of immunotherapy on HCC, several groups have attempt to use it as adjuvant therapy in order to reduce the recurrence rate. However the results are at the moment controversial. One can hypothetize that postoperative inflammation and liver regeneration can negatively impact the effect of the immunotherapy. Therefore, the administration of the treatmeent before surgical resection could overcome this issue.

Conditions

Hepato Cellular Carcinoma (HCC); Immunotherapy

Keywords

Neoadjuvant treatment; Hepatocellular carcinoma; atezolizumab; hepatectomy

Outcome Measures

Primary Outcomes (1)

• Difference in frequency of flow cytometry-assessed HCC-specific CD8+ cells in the periphery (PBMC) between patients with vs without ICI therapy prior to liver surgery

  We will assess the impact of ICI therapy on the frequency of HCC-specific CD8+ lymphocytes. The currently recruited patients will be compared to historical patients without ICI treatment. After flow cytometry sorting, bulk RNA sequencing of CD8+ cells will be performed. The SEQTR method will define the frequency of HCC-specific TCR.

  Four years

Secondary Outcomes (3)

• Tumor microenvironment changes induced by ICI therapy

  four years

• Overall survival and recurrence free survival

  four years

• Tumor burden

  Four years

Study Arms (2)

Treated group. Patients receiving immunotherapy before surgical resection of their HCC

EXPERIMENTAL

Drug: Atezolizumab

Control group

NO INTERVENTION

Patients undergoing surgical resection for HCC without any neoadjuvant treatment

Interventions

Atezolizumab DRUG

Patients will receive two doses of atzolizumab 6 and 3 weeks before surgery

Treated group. Patients receiving immunotherapy before surgical resection of their HCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult patients undergoing liver resection for HCC at the Geneva University Hospitals (HUG), with prior informed and signed consent.
• Patients will require to be eligible for surgical resection according to the BCLC guidelines (very early to early stage with preserved liver function and good patient condition) (4).
• The control group will include data from the patients in our ongoing research project (study protocol 2023-02372), undergoing liver resection without prior ICI therapy (n = 30).

You may not qualify if:

• Patients who do not ultimately undergo liver resection due to unforeseen reasons (this happens rarely, such as in the presence of unexpected HCC progression discovered during surgery).
• Patients with an ongoing pregnancy (an unlikely event, as non-surgical HCC treatments would be prioritized in such cases).
• Patients unable to follow procedures due to language barriers, insufficient comprehension of project language, or unable to give consent.
• Patients \<18 years.
• Patients with medical history of allergy or severe AEs to ICI therapy
• Pregnant and/or breastfeeding women. Lactating women should stop lactation or will be excluded from the study as breastfeeding under atezolizumab is not recommended. Furthermore, breastfeeding is not recommended for at least 5 months after the last dose.
• Immunosuppressed patients and patients with haematological disorder leading to a deficient immunity
• Patients with hepatic and/or cardiovascular deficiencies that contra-indicate surgery. Compensated cirrhotic patients are expected and will be included in the study as no dosage modification of the atezolizumab is required for these patients.
• Patients with untreated Hepatitis B and/or C or HIV. HIV patients under treatment with normal CD4 counts can be included. Hepatitis B and/or C patients under antiviral therapies can be included.
• Patients with history of inflammatory pneumopathy, active brain metastasis and patients treated with a systemic immunotherapy in the last 6 months.

Sponsors & Collaborators

• University of Geneva, Switzerland: lead

Study Sites (1)

Geneva University Hospitals

Geneva, 1205, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Charles-Henri Wassmer, MD-PhD

CONTACT

+41786682206; charles-henri.wassmer@hug.ch

Christian Toso, Professor

CONTACT

+41795533673; christian.toso@hug.ch

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: March 10, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)