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

Liver Transplant Clinical Trial

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

Status Not yet recruiting

Clinical 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. 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.

Clinical Trial 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 ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma Recurrent
• Liver Transplant
• Systemic Treatment

• NCT number: NCT06254248
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Manon Allaire, MD
• Phone: 142127064
• Email: manon.allaire@aphp.fr
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 15, 2024
• Completion date: December 15, 2028