A Clinical Trial of Firsekibart, Tislelizumab, and Lenvatinib in Patients With Unresectable, TP53-Mutated Hepatocellular Carcinoma

NCT07535840 | Not Yet Recruiting DMC

• 3 other identifiers: TJ-IRB2025121708237305282303185
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the effectiveness and safety of a combination therapy with Fuxinqibai monoclonal antibody, Tislelizumab, and Lenvatinib in patients with advanced, unresectable TP53-mutated hepatocellular carcinoma (HCC) who have previously failed systemic immunotherapy. Eligible patients will receive: Fuxinqibai 200 mg IV every 3 weeks Tislelizumab 200 mg IV every 3 weeks Lenvatinib 8 mg (≤60 kg) or 12 mg (\>60 kg) orally once daily Treatment will continue until disease progression, unacceptable toxicity, start of a new anticancer therapy, withdrawal of consent, or other protocol-defined reasons. Tumor response will be evaluated by RECIST v1.1 every 6 weeks, and confirmed after 4 weeks if response is observed. Safety will be monitored through adverse events and laboratory tests, graded according to NCI CTCAE v5.0. After treatment ends, patients will be followed every 6 weeks for tumor assessment and every 12 weeks for survival, until death, loss to follow-up, or withdrawal of consent. Primary Objective: To assess the objective response rate (ORR) of the combination therapy. Secondary Objectives: To evaluate overall efficacy, safety, and explore potential biomarkers predicting treatment response.

Conditions

HCC - Hepatocellular Carcinoma; TP53 Gene Mutation; Unresectable; Resistant Cancer

Keywords

Firsekibart; Tislelizumab; Lenvatinib; TP53-mutant hepatocellular carcinoma; Unresectable HCC; Advanced liver cancer; Single-arm study

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR) per RECIST v1.1

  The proportion of patients achieving complete response (CR) or partial response (PR) as assessed by blinded independent central review (BICR) according to RECIST v1.1 criteria. Responses must be confirmed at least 4 weeks after initial documentation.

  From first dose of study treatment until disease progression, start of new anti-tumor therapy, withdrawal of consent, or death, up to 24 months.

• Objective Response Rate (ORR) in patients with unresectable TP53-mutant advanced HCC

  Proportion of participants achieving complete response (CR) or partial response (PR) according to RECIST v1.1 criteria, confirmed by imaging at least 4 weeks after the initial response. Assessments include CT or MRI scans performed every 6 weeks (±7 days) during treatment.

  From first dose of study treatment until disease progression, start of new anti-tumor therapy, withdrawal of consent, or death, up to 24 months.

Study Arms (1)

Firsekibart Combined with Tislelizumab and Lenvatinib in Advanced TP53-Mutated Unresectable HCC

EXPERIMENTAL

articipants will receive Firsekibart 200 mg IV on Day 1 every 3 weeks, followed 1 hour later by Tislelizumab 200 mg IV on Day 1 every 3 weeks, and Lenvatinib orally once daily at 8 mg for patients ≤60 kg or 12 mg for patients \>60 kg. Treatment continues until disease progression, unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, or other protocol-specified discontinuation criteria.

Drug: Firsekibart + Tislelizumab + Lenvatinib

Interventions

Firsekibart + Tislelizumab + Lenvatinib DRUG

Participants will receive Firsekibart 200 mg IV on Day 1 every 3 weeks, followed 1 hour later by Tislelizumab 200 mg IV on Day 1 every 3 weeks, and Lenvatinib orally once daily (8 mg for ≤60 kg or 12 mg for \>60 kg). Treatment continues until disease progression, unacceptable toxicity, initiation of new anti-tumor therapy, withdrawal of consent, or other protocol-specified discontinuation criteria.

Firsekibart Combined with Tislelizumab and Lenvatinib in Advanced TP53-Mutated Unresectable HCC

Eligibility Criteria

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

You may qualify if:

• Ability to understand and sign written informed consent prior to any study-related procedures.
• Age ≥18 years at the time of signing informed consent.
• Histologically or cytologically confirmed advanced or unresectable hepatocellular carcinoma (HCC).
• Documented disease progression after prior systemic immunotherapy, including at least one PD-(L)1 inhibitor.
• Confirmed TP53 mutation in fresh liver tumor tissue by central laboratory testing.
• Determined by liver tumor MDT to be unsuitable for curative surgery (R0 resection not feasible, insufficient normal liver volume, or other criteria).
• BCLC stage B or C.
• At least one measurable lesion per RECIST v1.1 confirmed by BICR.
• ECOG performance status 0-1.
• Child-Pugh class A within 7 days prior to randomization.
• Adequate organ and bone marrow function within 7 days prior to enrollment:
• ANC ≥1.5×10\^9/L, Platelets ≥75×10\^9/L, HGB ≥9 g/dL
• TBIL ≤2×ULN, ALT/AST ≤5×ULN, Albumin ≥28 g/L, ALP ≤5×ULN
• Creatinine ≤1.5×ULN or CCr ≥50 mL/min, urine protein \<2+ (or 24-h urine protein \<1 g if baseline ≥2+)
• INR ≤2.3 or PT prolongation ≤6 sec

You may not qualify if:

• Candidates suitable for local curative therapy.
• Mixed liver tumors containing sarcomatoid or intrahepatic cholangiocarcinoma components.
• Hematologic malignancies.
• History of hepatic encephalopathy or prior liver transplantation.
• Symptomatic pleural effusion, ascites, or pericardial effusion requiring drainage; asymptomatic small effusions allowed.
• Active HBV (HBV DNA \>2000 IU/mL) or HCV (HCV RNA \>10\^3 copies/mL) infection; co-infection HBsAg+/HCV Ab+ excluded.
• CNS metastases.
• Significant recent variceal bleeding (within 6 months).
• Life-threatening hemorrhagic events within 3 months.
• Significant thromboembolic events within 6 months.
• Use of high-dose aspirin (\>325 mg/day) or other platelet inhibitors within 2 weeks prior to first dose.
• Unresolved grade ≥2 toxicities from prior therapies (excluding hair loss or asymptomatic lab abnormalities).
• Symptomatic heart failure NYHA II-IV or LVEF \<50%.
• Uncontrolled arrhythmias or congenital long QT syndrome, QTc \>500 ms.
• Active bleeding disorders or on thrombolytic therapy.

Sponsors & Collaborators

• Tongji Hospital: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

tislelizumab; lenvatinib

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 Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: This is an open-label study; no participants, care providers, investigators, or outcomes assessors are masked
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is an open-label, single-arm interventional study designed to evaluate the efficacy and safety of Firsekibart combined with Tislelizumab and Lenvatinib in patients with unresectable, advanced TP53-mutated hepatocellular carcinoma (HCC) who have progressed after prior systemic immunotherapy. All enrolled participants will receive the same combination therapy, with tumor response assessed every 6 weeks according to RECIST v1.1 criteria and safety monitored throughout the study.

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 17, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share