Tislelizumab Consolidation After Liver-Directed Therapy for Hepatocellular Carcinoma

NCT05366829 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 072105Pro2021001725
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 2

Brief Summary

The investigators hypothesize that the addition of Tislelizumab after definitive local therapy for locally advanced inoperable Hepatocellular carcinoma (HCC) will synergize with local therapy as well as treat micro metastatic disease and improve one year progression-free survival rates for participants and optimize local control.

Conditions

Carcinoma, Hepatocellular; Liver Cell Carcinoma

Keywords

Liver-Directed Therapy; Tislelizumab; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety as assessed by number of participants experiencing adverse events

  Number of participants experiencing adverse events grade three or higher, as defined by Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Severity is a measure of intensity (eg, grade of a specific AE, mild \[Grade 1\], moderate \[Grade 2\], severe \[Grade 3\], or life-threatening \[Grade 4\]), whereas seriousness is classified by the criteria based on the regulatory definitions. Seriousness serves as the guide for defining regulatory reporting obligations from the Investigator Sponsor to applicable regulatory authorities as described in CTCAE version 5.0.

  48 months

Secondary Outcomes (1)

• Response and progression will be evaluated in this trial using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee (v1.1).

  48 months

Study Arms (1)

Tislelizumab in conjunction with radiation therapy

EXPERIMENTAL

Participants will receive local therapy including TACE+ RT or Ablation (tumors with incomplete ablation) + RT or RT alone (for patients not eligible for TACE or Ablation) and will be screened for eligibility prior to enrollment. Once eligibility has been confirmed, Tislelizumab will be started before radiation therapy and will continue after radiation therapy. Participants who do not receive Tislelizumab for a total of two cycles will be replaced and interpreted for only toxicity analysis.

Drug: Tislelizumab

Interventions

Tislelizumab DRUG

Tislelizumab (also known as BGB A317) is a humanized, immunoglobulin G4 (IgG4)-variant monoclonal antibody against programmed cell death protein-1 (PD-1) under clinical development for the treatment of several human malignancies. Tislelizumab consolidation therapy after radiation therapy can capitalize on the immunomodulatory effect of radiotherapy and improve tumor responses and patient outcomes.

Tislelizumab in conjunction with radiation therapy

Eligibility Criteria

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

You may qualify if:

• Each patient eligible to participate in this study must meet all the following criteria:
• Written informed consent
• Primary diagnosis of HCC, planned to receive radiation, treatment naïve to systemic therapy for HCC, prior TACE permitted
• Hepatocellular carcinoma diagnosis by histologic findings and/or imaging criteria of LI-RADS 5
• Eastern Cooperative Oncology Group performance status score of 0-2
• Age\>/=18 years
• Child-Pugh class A liver function or B7, BCLC A-C or deemed not a candidate for surgery or liver transplantation
• No extrahepatic metastasis detected on CT chest with or without IV contrast, abdomen and pelvis with IV and oral contrast (triphasic-if feasible based on kidney function), or MRI abdomen/liver and chest CT.
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 6 months after the last dose of tislelizumab, and have a negative urine or serum pregnancy test ≤ 7 days of first dose of study drug
• Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 6 months after the last dose of tislelizumab. Males must agree not to donate or bank sperm during treatment with tislelizumab and for \> 6 months after treatment stop.
• Must have 1 target lesion measurable in 1 dimension according to RECIST 1.1.
• Demonstrate adequate bone marrow and organ function as defined below:
• Hematologic - Absolute neutrophil count (ANC) ≥ 1,500/mcL, Hemoglobin \> 8.5 g/dL, Platelet count ≥ 75,000/mcL
• Renal - Serum creatinine OR calculated\* serum creatinine clearance (GFR can be used in place of creatinine or creatinine clearance) ≤ 1.5x upper limit of normal (ULN) OR ≥ 30 mL/min for participants with creatinine levels \> 1.5x institutional ULN
• Calculate serum creatinine clearance using the standard Cockcroft-Gault formula.

You may not qualify if:

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• Prior radiotherapy to the region of the liver that would result in excessive doses to normal tissues due to overlap of radiation therapy fields
• Prior selective internal radiotherapy/hepatic arterial Yttrium therapy, at any time
• Severe, active co-morbidity as per investigator
• More than five discrete intrahepatic parenchymal foci of definite HCC or left/right or main portal vein thrombus
• Direct tumor extension into the stomach, duodenum, small bowel or large bowel
• Measurable common or main branch biliary duct involvement with HCC
• Extrahepatic metastases or malignant nodes (that enhance with typical features of HCC) \> 3.0 cm, in sum of maximal diameters (e.g. presence of one 3.4 cm metastatic lymph node or two 2 cm lung lesions).
• Note: benign non-enhancing periportal lymphadenopathy is not unusual in the presence of hepatitis and is permitted, even if the sum of enlarged nodes is \> 2.0 cm.
• Prior liver transplant
• HIV positive
• Immunodeficiency requiring chronic systemic therapy or that may relapse
• Participants who have received prior immunotherapy.
• Participants with clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control
• a. Note: Participants with ascites who require pharmacologic intervention (e.g. diuretics) to maintain symptomatic control and who have been on stable doses of diuretics for two months days prior to the first dose of study treatment are eligible.

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• BioGene Pharmaceutical Ltd.: collaborator
• Natera, Inc.: collaborator

Study Sites (2)

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10451, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab

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

Study Officials

• Salma Jabbour, MD

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Salma Jabbour, MD

CONTACT

732-253-3961; jabbousk@cinj.rutgers.edu

Patrick Boland, MD

CONTACT

732-235-6628; pb564@cinj.rutgers.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Radiation Oncology

Model Details: This study is a single-arm open-label phase II clinical trial to evaluate safety of the sequence of definitive therapy followed by Tislelizumab in participants with locally advanced unresectable hepatocellular carcinoma.

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 9, 2022
• Study Start: July 25, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)