Atezolizumab plus bevacizumab for recurrent advanced hepatocellular carcinoma in liver transplant recipients
Safety of Atezolizumab-Bevacizumab in Liver Transplanted Patients With Advanced Hepatocellular Carcinoma
This trial will see if the cancer drug combination atezolizumab plus bevacizumab is safe for adults whose hepatocellular carcinoma has recurred after a liver transplant.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 50 (estimated) |
| Ages | 18 Years to 90 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | atezolizumab, bevacizumab, immunotherapy |
| Locations | 10 sites (Clichy and 9 other locations) |
| Trial ID | NCT06254248 on ClinicalTrials.gov |
What this trial studies
This is an open-label, multicenter, single-arm two-stage phase 2 trial testing first-line atezolizumab‑bevacizumab in adult liver transplant recipients with unresectable recurrent advanced HCC. Patients will receive the drug combination alongside a standardized immunosuppressive regimen intended to reduce the risk of graft rejection. The primary endpoint is the rate of biopsy-confirmed acute cellular rejection at 6 months, with additional safety follow-up to 24 months and treatment end. Secondary endpoints include progression-free survival, overall survival, objective response rate, duration of response, and patient-reported quality of life, and outcomes will be compared to an existing historical cohort treated with TKIs.
Who should consider this trial
Good fit: Adults aged 18–89 who underwent liver transplantation at least 6 months earlier, now have unresectable recurrent advanced HCC with at least one measurable untreated lesion, and meet required blood and organ function criteria are the intended candidates.
Not a fit: Patients within 6 months of transplant, those with active graft dysfunction or high rejection risk, inadequate organ function, or contraindications to immunotherapy or bevacizumab are unlikely to benefit or may be excluded.
Why it matters
Potential benefit: If shown to be safe, this approach could expand first-line treatment options and potentially improve disease control and survival for liver-transplanted patients with recurrent HCC.
How similar studies have performed: Atezolizumab plus bevacizumab produced improved survival and acceptable tolerance in the Imbrave150 trial for non‑transplanted advanced HCC patients, but liver transplant recipients were excluded so safety in this group is untested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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 * 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
Where this trial is running
Clichy and 9 other locations
- Hôpital Beaujon — Clichy, France (Recruiting)
- Hôpital Henri-Mondor — Créteil, France (Recruiting)
- Hôpital Claude Huriez - CHU de Lille — Lille, France (Recruiting)
- Lyon - Hôpital Croix Rousse — Lyon, France (Recruiting)
- CHU Montpellier - Hôpital Saint Eloi — Montpellier, France (Recruiting)
- Hôpital Pitié-Salpêtrière — Paris, France (Recruiting)
- CHU Rennes - Hôpital Pontchaillou — Rennes, France (Recruiting)
- Hôpital de Hautepierre - Strasbourg — Strasbourg, France (Recruiting)
- CHU Tours - Hôpital Trousseau — Tours, France (Recruiting)
- Hôpital Paul Brousse — Villejuif, France (Recruiting)
Study contacts
- Study coordinator: Manon Allaire, MD
- Email: manon.allaire@aphp.fr
- Phone: 142127064
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.