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

NCT06254248 | Recruiting Phase 2 DMC

• 2 other identifiers: APHP2308992024-514400-14-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief 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. 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.

Conditions

Liver Transplant; Systemic Treatment; Hepatocellular Carcinoma Recurrent

Keywords

HCC; systemic therapy; graft rejection; immunotherapy; Atezolizumab-Bevacizumab

Outcome Measures

Primary Outcomes (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

  6 months

Secondary Outcomes (9)

• Rate of Acute Cellular Rejection (ACR) at 24 months

  24 months

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

  at the end of treatment

• Progression Free Survival (PFS)

  between the inclusion and 24 months after the last inclusion

• Overall survival (OS)

  between the inclusion and 24 months after the last inclusion

• Objective Response Rate (ORR)

  12 months

Study Arms (1)

Atezo-Beva combination

EXPERIMENTAL

first-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

Drug: Systemic therapy

Interventions

Systemic therapy DRUG

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.

Atezo-Beva combination

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (10)

Hôpital Beaujon

Clichy, 92110, France

RECRUITING

Hôpital Henri-Mondor

Créteil, 94010, France

RECRUITING

Hôpital Claude Huriez - CHU de Lille

Lille, 59037, France

RECRUITING

Lyon - Hôpital Croix Rousse

Lyon, 69004, France

RECRUITING

CHU Montpellier - Hôpital Saint Eloi

Montpellier, 34295, France

RECRUITING

Hôpital Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

CHU Rennes - Hôpital Pontchaillou

Rennes, 35033, France

RECRUITING

Hôpital de Hautepierre - Strasbourg

Strasbourg, 67200, France

RECRUITING

CHU Tours - Hôpital Trousseau

Tours, 37044, France

RECRUITING

Hôpital Paul Brousse

Villejuif, 94800, France

RECRUITING

Central Study Contacts

Manon Allaire, MD

CONTACT

142127064; manon.allaire@aphp.fr

Anne Bissery

CONTACT

142162432; anne.bissery@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: February 12, 2024
• Study Start: January 22, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 10, 2026

Record last verified: 2026-03

Locations

FR (10)