Atezolizumab and Bevacizumab in Combination With Y^90 Radioembolization in HCC for Liver Transplant

NCT07059494 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: STUDY-24-01566PRMC-24-146
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A single institution, single arm, two-cohort feasibility trial to evaluate the combination of locoregional Y\^90 therapy with systemic atezolizumab and bevacizumab, in participants presenting with hepatocellular carcinoma (HCC) 1) within Milan Criteria (MC) with AFP ≥ 400 ng/ml as a means of bridge therapy prior to transplant, 2) beyond the Milan Criteria (MC) (within USCF DS criteria and all comers), as a means of downstaging prior to liver transplantation.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants with Response to treatment

  Cohort A Proportion of participants downstaging to within Milan Criteria as assessed by the rate of radiographic response via CT/MRI pre transplantation (efficacy window of assessment = 9 months from first cycle of Y\^90) Cohort B Response rate to treatment in participants within MC with AFP ≥ 400 ng/ml defined by CT/MRI and a decrease in AFP ≥ 50 percent (efficacy window of assessment = 9 months from first cycle of Y\^90)

  9 months from first cycle of Y^90

Secondary Outcomes (9)

• Adverse Events

  1 year

• Pathological response

  At time of transplant procedure

• Disease progression

  From time of treatment start to time of disease progression (at 1 year or upon occurrence of event, whichever comes first)

• Recurrence-free survival (RFS)

  From treatment Day 1 to post-transplant Year 1

• Post-transplant recurrence rate

  From Day 1 post-transplant to Year 1 post-transplant

Study Arms (2)

Cohort A: participants beyond Milan Criteria upon enrollment

EXPERIMENTAL

Atezolizumab and Bevacizumab in Combination with Y\^90 Radioembolization

Drug: Atezolizumab; Drug: Bevacizumab; Radiation: Y^90 Radioembolization

Cohort B: participants within Milan Criteria with AFP ≥ 400 ng/ml at enrollment.

EXPERIMENTAL

Atezolizumab and Bevacizumab in Combination with Y\^90 Radioembolization

Drug: Atezolizumab; Drug: Bevacizumab; Radiation: Y^90 Radioembolization

Interventions

Atezolizumab DRUG

Atezolizumab is an immune checkpoint inhibitor. It is a monoclonal antibody that works by binding to the protein PD-L1 on the surface of some cancer cells, which keeps cancer cells from suppressing the immune system. It is indicated for usage in Non-Small Cell Lung Cancer (NSCLC), Small Cell Lung Cancer (SCLC), Hepatocellular Carcinoma (HCC), Melanoma, and Alveolar Soft Part Sarcoma (ASPS).

Cohort A: participants beyond Milan Criteria upon enrollment; Cohort B: participants within Milan Criteria with AFP ≥ 400 ng/ml at enrollment.

Bevacizumab DRUG

Bevacizumab is a vascular endothelial growth factor inhibitor indicated for the treatment of metastatic colorectal cancer, in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment. It is also indicated for the treatment of metastatic colorectal cancer, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy for second-line treatment in participants who have progressed on a first-line bevacizumab product-containing regimen.

Cohort A: participants beyond Milan Criteria upon enrollment; Cohort B: participants within Milan Criteria with AFP ≥ 400 ng/ml at enrollment.

Y^90 Radioembolization RADIATION

Radioembolization is a minimally invasive procedure that combines embolization and radiation therapy to treat cancers in the liver. Tiny beads filled with a radioactive isotope are placed inside the blood vessels that supply a tumor. This blocks the supply of blood to the cancer cells and delivers a high dose of radiation to the tumor while sparing normal tissue. It can help extend the lives of participants with inoperable tumors and improve their quality of life.

Cohort A: participants beyond Milan Criteria upon enrollment; Cohort B: participants within Milan Criteria with AFP ≥ 400 ng/ml at enrollment.

Eligibility Criteria

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

You may qualify if:

• Signed Informed Consent Form
• Age ≥18 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• Newly diagnosed, biopsy-proven hepatocellular carcinoma (HCC) that is histologically or cytologically confirmed
• Availability of a representative tumor specimen that is suitable for determination of PD-L1 status via central testing. A formalin-fixed paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 10-15 slides (15 slides preferred) slides containing unstained, freshly cut, serial sections should be submitted along with an associated pathology report prior to study enrollment. If archival tumor tissue is unavailable or is determined to be unsuitable for required testing, tumor tissue must be obtained from a biopsy performed at screening. Availability of a representative tumor specimen for exploratory biomarker research. Newly diagnosed, biopsy-proven hepatocellular carcinoma (HCC) either outside of the Milan Criteria (MC), or within the MC, with high risk disease as defined by alpha-fetoprotein (AFP) ≥400 ng/mL, and also fulfilling the criteria below.
• Within MC with AFP ≥ 400 ng/ml
• single lesion (≤5cm) or 3 lesions (≤3cm)
• Absence of vascular invasion or extra-hepatic disease based on cross-sectional imaging
• Child-Pugh Score of A/B7 (without ascites)
• UNOS-DS Protocol
• HCC exceeding UNOS T2 criteria but meeting one of the following:
• Single lesion ≤ 8 cm
• or 3 lesions each ≤ 5 cm with the sum of the maximal tumor diameters ≤8 cm
• or 5 lesions each ≤ 3 cm with the sum of the maximal tumor diameters ≤ 8 cm
• Absence of vascular invasion or extra-hepatic disease based on cross-sectional imaging

You may not qualify if:

• AFP ≥ 1000 ng/ml
• Pathologically mixed tumors, vascular invasion or extra-hepatic disease based on cross-sectional imaging
• History of leptomeningeal disease
• Uncontrolled tumor-related pain
• o Participants requiring pain medication must be on a stable regimen at study entry.
• Severe pulmonary disease, uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) o Participants with indwelling catheters (e.g., PleurX®) are allowed
• Uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN)
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, uncontrolled HIV, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis (protocol lists a more comprehensive list of autoimmune diseases and immune deficiencies), with the following exceptions:
• Participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
• Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
• Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10 percent of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Parissa Tabrizian, MD

  Mount Sinai Liver Cancer Program

  PRINCIPAL INVESTIGATOR

• Josep Llovet, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brandy Haydel

CONTACT

(212) 241-0255; Brandy.Haydel@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Surgery

Model Details: Feasibility study

Study Record Dates

• First Submitted: June 17, 2025
• First Posted: July 10, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. To achieve aims in the approved proposal. Specify Other Mechanism Contact PI Parissa.Tabrizian@mountsinai.org

Locations

US (1)