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Liver TransplantPhase 2IMMUNO-THNCT06254248

Safety of Atezolizumab-Bevacizumab in Liver Transplanted Patients With Advanced Hepatocellular Carcinoma

A Phase 2 study testing Systemic therapy in people with Liver Transplant and Hepatocellular Carcinoma Recurrent, run by Assistance Publique - Hôpitaux de Paris at 10 sites in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The prognosis of liver transplanted (LT) patients with recurrence of hepatocellular carcinoma (HCC), especially those with progression after locoregional treatment or advanced HCC, remains poor. Read more about this study

Who is it for?
Ages 18 to 90 years
What is being tested?
Systemic therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
10 sitesFrance
Study dates
22 Jan 2026to 1 Jan 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • All patients over 18 and under 90 years old:
  • who underwent LT more than 6 months ago (to prevent the higher risk of ACR which exists within the first months after LT and to deal with populations with a lowered immunosuppressive regimen long after LT)
  • with HCC recurrence diagnosis according to the EASL diagnostic criteria (33)
  • with advanced HCC not accessible to surgery and locoregional treatment
  • with at least one measurable untreated lesion
  • With a proposal for Atezo-Beva in first line treatment made in a multidisciplinary meeting
Show all 21Show fewer
  • Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment, unless otherwise specified:
  • ANC ≥ 1.5 x 109/L (1500/µL) without granulocyte colony-stimulating factor support
  • Lymphocyte count ≥ 0.5 x 109/L (500/µL)
  • Platelet count ≥ 75 x 109/L (75,000/µL) without transfusion
  • Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused to meet this criterion.
  • AST, ALT ≤ 5 x upper limit of normal (ULN)
  • Serum bilirubin ≤ 3x ULN
  • creatinine clearance≥40 mL/min (calculated using the Cockcroft-Gault formula)
  • For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 2x ULN
  • Urine dipstick for proteinuria < 2+ (within 7 days prior to initiation of study treatment). Patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate <1 g of protein in 24 hours
  • ECOG Performance Status of 0 or 1
  • For women of childbearing potential and men: agreement to remain abstinent or use effective contraception during treatment and at least :
  • 5 months after the end of the treatment with atezolizumab,
  • 6 months after the end of the treatment with bevacizumab
  • Child-Pugh class A

Who cannot join

  • History of ACR within 3 months before starting Atezo-Beva treatment
  • Banff score for ACR ≥ 3 on liver biopsy performed before the initiation of the treatment
  • Pregnant or breastfeeding woman
  • Patient not affiliated to a beneficiary or entitled social security scheme or to the PUMA
  • Patient not having signed consent
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT-scan
Show all 22Show fewer
  • History of malignancy other than HCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
  • A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment.
  • Inadequately controlled arterial hypertension (defined as systolic blood pressure (BP) ≥ 160 mmHg and/or diastolic blood pressure > 100 mmHg), based on an average of ≥ 3 BP readings on ≥ 2 sessions Anti-hypertensive therapy to achieve these parameters is allowable.
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses
  • Hypersensitivity to the active substance or to any of the excipients of the SmPC of bevacizumab and the SmPC of atezolizumab
  • Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
  • Prior arterial thromboembolic reactions including cerebrovascular accidents, transient ischaemic attacks and myocardial infarctions;
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • In case of proteinuria > 1g in 24 hours
  • History of leptomeningeal disease
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

Trial locations and contacts

10 sites in 1 country. Contact the study team or a site near you to ask about taking part.

10 sites in 1 country

France10 sites, 10 recruiting
  • Hôpital Beaujon

    Clichy, 92110

    Mohamed BOUATTOUR, MD, 140875614 ext. +33, mohamed.bouattour@aphp.fr

    Recruiting
  • Hôpital Henri-Mondor

    Créteil, 94010

    Giuliana AMADDEO, MD, 149812367 ext. +33, giuliana.amaddeo@aphp.fr

    Recruiting
  • Hôpital Claude Huriez - CHU de Lille

    Lille, 59037

    Massih NINGARHARI, MD, 320444337 ext. +33, massih.ningarhari@chu-lille.fr

    Recruiting
  • Lyon - Hôpital Croix Rousse

    Lyon, 69004

    Teresa ANTONINI, MD, 426732654 ext. +33, teresa.antonini@chu-lyon.fr

    Recruiting
  • CHU Montpellier - Hôpital Saint Eloi

    Montpellier, 34295

    Stéphanie FAURE, MD, 467337064 ext. +33, s-faure@chu-montpellier.fr

    Recruiting
  • Hôpital Pitié-Salpêtrière

    Paris, 75013

    Manon ALLAIRE, MD, 142127064 ext. +33, manon.allaire@aphp.fr

    Recruiting
  • CHU Rennes - Hôpital Pontchaillou

    Rennes, 35033

    Thomas UGUEN, MD, 299282525 ext. +33, thomas.uguen@chu-rennes.fr

    Recruiting
  • Hôpital de Hautepierre - Strasbourg

    Strasbourg, 67200

    Camille BESCH, MD, 388127268 ext. +33, camille.besch@chru-strasbourg.fr

    Recruiting
  • CHU Tours - Hôpital Trousseau

    Tours, 37044

    Ephrem SALAME, MD, PhD, 247475937 ext. +33, e.salame@chu-tours.fr

    Recruiting
  • Hôpital Paul Brousse

    Villejuif, 94800

    Olivier ROSMORDUC, MD, PhD, 145596540 ext. +33, olivier.rosmorduc@aphp.fr

    Recruiting

Other trials in France

About this study

The prognosis of liver transplanted (LT) patients with recurrence of hepatocellular carcinoma (HCC), especially those with progression after locoregional treatment or advanced HCC, remains poor. Current treatment modalities involve tyrosine kinase inhibitors (TKIs) characterized by a low response rate and often poor tolerability. Encouraging findings from the Imbrave 150 study, demonstrating increased survival rates coupled with favorable treatment tolerance, prompt the investigators to consider the potential of offering the combination of treatment with Atezolizumab-Bevacizumab (Atezo-Beva) to patients with LT. No data regarding the safety and efficacy of this new combination are available for patients with LT as they were not included in Imbrave 150. Immunosuppression after LT is low when compared to essentially all other organ recipients, liver recipients are considered with lower immunological risk. However, the use of ICIs has been associated with a risk of hepatic rejection in LT patients. In this study, in order to prevent acute cellular rejection (ACR) occurrence, we propose to adopt a standardized immunosuppressive regimen closed to the one used immediately after LT but with lower therapeutic goals for tacrolimus and everolimus to allow immunotherapy treatment to be effective. The better tolerance of liver grafts will probably lead to less risk of rejection with Atezo-Beva than in other organ transplants.

Read the detailed description

Open-label multicentric single-arm two-stage phase 2 trial. Population: Adult LT patients with advanced HCC recurrence with indication to systemic treatment Primary objective: To study the safety (ACR on histology) at 6 months of the first-line Atezo-Beva combination in LT patients with recurrent HCC in association with a standardized immunosuppressive treatment to prevent the risk of liver graft rejection.

Primary endpoint: Rate of Acute cellular rejection (ACR) (defined by a Histological Banff score ≥ 5) at 6 months (confirmed by an external expert center).

Secondary objective:

To study the safety (ACR on histology) at 24 months and at the end of Atezo-Beva treatment in LT patients with recurrent HCC in association with a standardized immunosuppressive treatment to prevent the risk of liver graft rejection.

  • To assess the efficacy and tolerance of first-line Atezo-Beva combination in LT patients with advanced HCC in association with a standardized immunosuppressive treatment to prevent the risk of ACR based on:
  • the Progression Free Survival (PFS)
  • the Overall survival (OS)
  • the objective response rate (ORR) (complete and partial response)
  • the duration of response
  • the quality of life of the patients under Atezo-Beva treatment
  • To compare the efficacy (OS and PFS) of LT patients treated by Atezo- Beva treatment to an historical retrospective cohort of LT patients already available treated by TKI as first line (external arm comparison)
  • To assess the adverse events related to Atezo-Beva treatment in LT patients with recurrent advanced HCC.
  • To assess the evolution of the level of donor specific antibodies (DSA) during Atezo-Beva treatment and its association with ACR, PFS and OS.

Translational research/ancillary studies:

  • To assess the association before the first injection between the risk of ACR, PFS, OS and side effects and
  • the "Immunome" imaging on tumor sample and non-tumoral liver sample to quantify and regionalize immune populations on pathology (Multispectral Imaging, Mantra)
  • the Leukocyte DNA analysis to identify constitutional genetic variants
  • To assess the association before the first injection or just before the second injection and at 3 months between the risk of ACR, PFS, OS and side effects and
  • the "immunomonitoring" on blood sample (frequency and/or the phenotype of circulating immune cells)
  • the presence of tumors cells (liquid biopsies)
  • the presence of circulating tumor DNA and the type of mutations
  • the presence of circulating proteins
  • the profile of circulating exosomes
Being tested
Systemic therapy
Keywords
HCC, systemic therapy, graft rejection, immunotherapy, Atezolizumab-Bevacizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Systemic therapyDrug

    Atezolizumab-Bevacizumab every 3 weeks until progression or side effects in combination with Standardized immunosuppressive treatment:

    Tacrolimus (objective 5-7 ng/ml) Mycophenolate Mofetil 1000 mg per day Corticosteroids at least 5 mg per day Everolimus will be continued if already started before the inclusion (objective 5-7 ng/ml). If everolimus has not been started prior to inclusion, do not start it, but adopt the following protocol: corticoids + Tacrolimus + Cellcept.

Study groups in NCT06254248
Study groupRoleWhat they receive
Atezo-Beva combinationExperimentalfirst-line Atezo-Beva combination in LT patients with advanced HCC in association with a standardized immunosuppressive treatment to prevent the risk of acute cellular rejection
Receives: Drug: Systemic therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Rate of Acute cellular rejection (ACR) (defined by a Histological Banff score ≥ 5) at 6 months (confirmed by an external expert center)

    To study the safety (ACR on histology) at 6 months of the first-line Atezo-Beva combination in LT patients with recurrent HCC in association with a standardized immunosuppressive treatment to prevent the risk of liver graft rejection

    Measured: 6 months

Secondary outcomes (9)
  1. Rate of Acute Cellular Rejection (ACR) at 24 months

    Rate of ACR (defined by a Histological Banff score ≥ 5) at 24 months (confirmed by a second external expert center.

    Measured: 24 months

  2. Rate of Acute Cellular Rejection (ACR) at the end of Atezo-Beva treatment

    Rate of ACR (defined by a Histological Banff score ≥ 5) at 24 months and at the end of Atezo-Beva treatment (confirmed by a second external expert center.

    Measured: at the end of treatment

  3. Progression Free Survival (PFS)

    The Progression Free Survival (PFS) is defined as the time from inclusion to disease progression according to RECIST 1.1 on imaging (CT-scan) performed every 3 months or death from any cause, whichever occurred first.

    Measured: between the inclusion and 24 months after the last inclusion

  4. Overall survival (OS)

    The Overall survival (OS) defined by the time from inclusion to death from any cause

    Measured: between the inclusion and 24 months after the last inclusion

  5. Objective Response Rate (ORR)

    The Objective Response Rate (ORR) at 12 months is defined as the percentage of patients with a confirmed complete or partial response according to RECIST 1.1 criteria on imaging (CT-scan) performed every 3 months.

    Measured: 12 months

  6. Duration of response

    The Duration of response is defined by the time from first documentation of complete or partial response to disease progression or death according to RECIST 1.1 criteria on imaging (CT-scan) performed every 3 months.

    Measured: between the inclusion and 24 months after the last inclusion

  7. Time to deterioration of quality of life

    The time to deterioration of quality of life is defined as the time from inclusion to the first deterioration of quality of life as reported by the patient, with deterioration defined as a decrease from baseline of 10 points or more on the EORTC QLQ-C30 maintained for two consecutive assessments or a decrease of 10 points or more in one assessment followed by death from any cause within 3 weeks. Each quality of life evaluation will be reported by the patient using EORTC QLQ-C30 score fill formed every 6 months until 24 months after the initiation of the treatment.

    Measured: between the inclusion and 24 months after the last inclusion

  8. Type, frequency and severity of adverse events and serious adverse events

    They will be assessed on the basis of the nature, frequency and severity of adverse events according to NCI Common Terminology Criteria for Adverse Events, version 4.0. The management of side effects usually observed under immunotherapy will be managed according to the American Society of Clinical Oncology Clinical Practice Guidelines

    Measured: between the inclusion, at the end of Atezo-Bev treatment and up to 24 months

  9. Donor Specific Antibodies (DSA) median

    DSA will be assessed and correlation to ACR, the PFS and OS will be evaluated

    Measured: baseline and at Day 21, 3 Months 6 Months , 12 Months , 18 Months , 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2024
  2. Study start22 Jan 2026
  3. Primary completion1 Jan 2030 (estimated)
  4. Study completion1 Jan 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06254248
Sponsor's protocol ID
APHP230899
Other IDs
2024-514400-14-00
Acronym
IMMUNO-TH
Status last verified
Mar 2026
First submitted
12 Jan 2024
Last updated
10 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Systemic therapy in people with Liver Transplant and Hepatocellular Carcinoma Recurrent, run by Assistance Publique - Hôpitaux de Paris at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Manon Allaire, MD (142127064 ext. +33, manon.allaire@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Acute cellular rejection (ACR) (defined by a Histological Banff score ≥ 5) at 6 months (confirmed by an external expert center) (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.

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