Identification of an Immune Single Cell Transcriptomic Profile of Responder and Non-responder Hepatocellular Carcinoma Patients Treated With Immune-checkpoint Inhibitors (HCC RNA-seq)

The study aims to analyze blood samples from patients with advanced hepatocellular carcinoma who are receiving systemic treatment with immunotherapy. The objective is to determine whether treatment exposure leads to changes in the transcriptomic patterns of peripheral blood mononuclear cells (PBMCs), if these changes are associated with treatment response, and whether certain pre-treatment transcriptomic signatures can predict response to treatment.

As an exploratory objective, PBMCs derived from patients exposed to immune checkpoint inhibitors will be co-cultured with their paired tumor cells in organoid cultures. This aims to assess whether these preclinical 3D models correlate with clinical outcomes.

Study Overview

• Status: Recruiting
• Conditions: Advanced HCC Treated by Systemic Immunotherapy

Detailed Description

The primary pivotal objective of the study is to analyse the single cell transcriptome of peripheral blood mononuclear cells (PBMCs) in patients with HCC treated with immunotherapy to define if treatment exposure determines transcriptomic pattern changes and if some of these changes are associated with treatment response.

The secondary objective of the study is to investigate if some pre-treatment transcriptome signature of PBMCs is predictive of response and long-lasting response to treatment.

As an exploratory objective, the study investigators will analyse the interaction between patients' peripheral immune cells previously exposed to immune check-point inhibitors and their paired tumour cells in the organoid cultures.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Salvatore Corallo; Phone Number: +39 0382501557; Email: s.corallo@smatteo.pv.it

Study Locations

• Italy
  • Lombardy
    • Pavia, Lombardy, Italy, 27100
      • Recruiting
      • Fondazione IRCCS Policlinico San Matteo
      • Contact: Salvatore Corallo, MD; Phone Number: +39 0382501557; Email: s.corallo@smatteo.pv.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients treated with atezolizumab plus bevacizumab or tremelimumab single dose plus durvalumab (STRIDE regimen) as first-line treament for advanced HCC

Description

Inclusion Criteria:

1. diagnosis of advanced HCC treated with atezolizumab plus bevacizumab or tremelimumab single dose plus durvalumab (STRIDE regimen) as first-line treament
2. age ≥18 and <90 years at time of signing informed consent
3. Signed Informed Consent Form

Exclusion Criteria:

1. Life expectancy of <12 months due to concomitant diseases
2. Active or history of autoimmune disease or immune deficiency on inflammatory chronic diseases
3. Ongoing drug abuse

4. History of malignancy other than HCC within 3 years prior to study entry with the following exception:

   1. Completely resected malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate 90%) and without evidence of recurrence for > 3 years prior to study entry
   2. adequately treated non-melanoma skin carcinoma or lentigo maligna without evidence of metastases.
   3. adequately treated carcinoma in situ of the cervix without evidence of recurrence
   4. localised prostate cancer
   5. adequately treated non invasive or in situ urothelial cancers
5. evidence or history of positive HIV test
6. inability to comply with the study protocol, in the investigator's judgment

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Single cohort; Patients treated withi immune-check point inhibitor-based combinations as first-line treatment for advanced HCC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Analysis of the single cell profiling of peripheral blood mononuclear cells in patients with HCC treated with immunotherapy pre-therapy (T0) and the 3 months post-therapy (T3) to define if a difference between the two time points exists.	The single cell profiling of peripheral blood mononuclear cells in patients with HCC treated with immunotherapy will be analised at two type points: before starting therapy(T0), and the 3 months post-therapy (T3). The difference of single cell profiling of the two paired time-points will be analysed.	From enrollment untill 3 months after treatment start, (up to 120 days from study inclusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between transcriptome signature at baseline and treatment outcomes.	To define if there is a correlation between baseline transcriptome signatures and treatment outcomes (duration of response, median progression-free survival, median overall survival)	From enrollment to the time of best response to treatment, up to 24 months from enrollement
Correlation between baseline gene clusters and treatment responses	To identify baseline gene clusters that correlats with higher respose rates	From enrollment to the time of best response, up to 24 months from enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring the interacton between PBMCs and tumor tissue in 3D culture system.	To compare the percentage of apoptosis in tumor cells from patient-derived 3D culture systems of HCC, co-cultured with PBMC harvested after treatment with immune checkpoint inhibitors (ICIs), versus those co-cultured with baseline PBMCs collected at T0.	From enrollment untill 3 months after treatment start, (up to 120 days from study inclusion)

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Policlinico San Matteo di Pavia

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: September 22, 2025
• First Submitted That Met QC Criteria: November 28, 2025
• First Posted (Estimated): December 9, 2025

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: November 28, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: HCC Organoids; HCC PBMCs
• Other Study ID Numbers: 0014773/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Pending privacy protection evaluation

Drug and device information, study documents

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