TUDCA with camrelizumab and regorafenib for advanced hepatocellular carcinoma after anti‑PD‑1/PD‑L1 plus bevacizumab

Tauroursodeoxycholic Acid (TUDCA) Plus Camrelizumab and Regorafenib in Hepatocellular Carcinoma Previously Treated With Anti-PD1/PD-L1 and Bevacizumab: A Randomized, Phase 2 Study.

This trial tests whether adding TUDCA to camrelizumab and regorafenib helps people with advanced hepatocellular carcinoma that got worse after anti‑PD‑1/PD‑L1 plus bevacizumab.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 141 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: bevacizumab, Camrelizumab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07100392 on ClinicalTrials.gov

What this trial studies

This is a phase 2, open‑label, randomized three‑arm trial enrolling adults with advanced or unresectable hepatocellular carcinoma who progressed on prior anti‑PD‑1/PD‑L1 plus bevacizumab. Participants are randomized to receive regorafenib alone, regorafenib plus camrelizumab, or regorafenib plus camrelizumab with TUDCA, with tumor responses measured by RECIST v1.1 and safety monitored throughout. Key eligibility includes measurable disease, Child‑Pugh score 5–7, ECOG performance status 0–2, and controlled HBV when present. The study will compare efficacy outcomes (such as response rate and disease control) and adverse events across the arms.

Who should consider this trial

Good fit: Adults with locally advanced or metastatic unresectable HCC who progressed after prior anti‑PD‑1/PD‑L1 plus bevacizumab, with measurable disease, Child‑Pugh 5–7, ECOG ≤2, and controlled HBV when applicable.

Not a fit: Patients with poor liver function (Child‑Pugh >7), ECOG >2, uncontrolled HBV, or who have not had prior anti‑PD‑1/PD‑L1 plus bevacizumab are unlikely to be eligible or to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination including TUDCA could extend tumor control or survival for patients who stopped responding to anti‑PD‑1/PD‑L1 plus bevacizumab.

How similar studies have performed: Combining multikinase inhibitors like regorafenib with PD‑1 inhibitors has shown activity in HCC in prior studies, but adding TUDCA is a novel approach with limited prior clinical evidence.

Eligibility criteria

Inclusion Criteria:

* Written informed consent obtained.
* Age ≥ 18 years at time of study entry.
* Locally advanced or metastatic and/or unresectable HCC with diagnosis confirmed by histology/ cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic patients.
* Disease progression following prior anti-PD1/PD-L1 plus bevacizumab combination treatment for HCC.
* At least one measurable (per RECIST v1.1) target lesion that has not been previously treated with local therapy or, if the target lesion is within the field of previous local therapy, has subsequently progressed in accordance with RECIST v1.1.
* Child-Pugh scores 5-7, performance status (PS) ≤ 2 (ECOG scale).
* Subjects with chronic HBV infection must have HBV DNA viral load \< 100 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.
* Life expectancy of at least 12 weeks.
* Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥60 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula)
* Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
* Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.

Exclusion Criteria:

* Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
* Patients on a liver transplantation list or with advanced liver disease.
* History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
* Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
* Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
* Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
* Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
* Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to: a) history of interstitial lung disease b) Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) c) known acute or chronic pancreatitis d) active tuberculosis e) any other active infection (viral, fungal or bacterial) requiring systemic therapy f) history of allogeneic tissue/solid organ transplant g) diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of treatment. h) Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. i) Live vaccine within 30 days prior to the first dose of treatment or during study treatment. j) History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS.
* Medication that is known to interfere with any of the agents applied in the trial.
* Any other efficacious cancer treatment except protocol specified treatment at study start.
* Patient has received any other investigational product within 28 days of study entry.
* Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). \[Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner\]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital, Fudan University — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Peng Wang, MD

Conditions: Hepatocellular Carcinoma