Clinical Research Directory

FOG-001 in Locally Advanced or Metastatic Solid Tumors

The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic solid tumors.

Optimizing Y90 Therapy for Radiation Lobectomy

HCC resection candidates with inadequate future liver remnant will be enrolled in this study. They will be treated with Y90 radioembolization to help grow the liver enough to undergo liver resection. There will be 2 Patient Groups. The first group of patients will be treated with Y90 dose and embolic load as per standard-of-care. The second group of patients will be treated with the optimal Y90 dose and embolic load found in Patient Group 1.

Pembrolizumab in Hepatocellular Carcinoma

This is a single-arm Phase II trial of pembrolizumab in patients with hepatitis B virus-related hepatocellular carcinoma with parallel study on baseline and serial change in the immune environment. Subjects should have a confirmed diagnosis of HCC (in accordance with the AASLD guideline) and confirmed chronic infection with hepatitis B virus as defined by positivity for HBsAg. Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. They must have disease not amenable to a curative treatment approach or loco-ablation. Subject must be fit and agreeable with baseline and post-treatment biopsy of tumor. Subjects must have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 and adequate organ functions. 30 subjects will be enrolled to receive pembrolizumab 200 mg IV every 3 weeks(Q3W). Pre-treatment and on-treatment biopsy after 2 cycles of Pembrolizumab will be preformed. Treatment will be stopped when progression of disease or intolerable toxicity occurs. The primary objectives of this trial are to study the efficacy and safety of pembrolizumab in patients with HBV-related HCC and to study the serial change in RNA expression of immune-related gene panel in post-treatment biopsy tissue. The secondary objectives of this trial are to study the serial change in cytokine profile between pre-treatment and post-treatment samples, to study the PD-L1 immunohistochemical (IHC) expression in tumor sample at baseline and post-treatment tissue samples and to study the presence of tumor infiltrating lymphocytes in the baseline and post-treatment tumor samples. The exploratory objective of this trial is to evaluate the possibility of using baseline and the serial change in RNA expression of immune-related gene panel or PD-L1/2 IHC to predict treatment response.

SBRT in HCC With Oligoprogression on First-line Immunotherapy

HCC is a huge healthcare burden in Hong Kong and is one of the top 5 cancers in terms of incidence and mortality in Hong Kong. Patients with advanced HCC are treated with immunotherapy-based as first-line treatment as a standard of care. At the moment, there is limited evidence to guide subsequent treatments after patients progressed on immunotherapy. Oligoprogression is a term used to describe patients who had limited progression (usually less than 3 sites) on systemic therapy, with the rest of the lesions controlled. Previous studies in non-HCCs have shown that addition of locoregional treatment (e.g. radiotherapy) may prolong the use of systemic therapy, resulting in improved survival, but this has been relatively unexplored for HCC. In this prospective, single-arm study, we aim to evaluate the treatment outcome, efficacy and safety of the addition of radiotherapy to oligoprogressive sites for patients who had limited progression on First-line Immunotherapy.

Cabozantinib in Hepatocellular Carcinoma

There have been lack of clinical studies on the role of drug treatment in patients who develop progressive disease with immune checkpoint inhibitors. Amongst HCC patients who become intolerant or refractory to sorafenib, cabozantinib has been shown by phase III clinical trial (CELESTIAL) to prolong the overall survival of patients, as compared to placebo. It is expected more patients will be treated with immune checkpoint inhibitors in future, hence it is clinically important to study the efficacy and toxicity of cabozantinib after treatment with immune checkpoint inhibitors. Further, both MET activation and upregulation of regulatory T cells are implicated in resistance mechanism to immune checkpoint inhibitors. Immuno-modulatory effects of cabozantinib have been described in vitro and in murine models for several cancers. Moreover, cabozantinib appears to exert its effect on regulatory T cells (Tregs) via the HGF/c-Met pathway, where this receptor signaling cascade mediates multiple immune cell functions. HGF was shown to suppress DC function and in turn induce Tregs (CD4+ CD25+ FoxP3) in a murine central nervous system (CNS) autoimmunity model. HGF cultured monocytes differentiate into monocytic cells that produce soluble factors that favor immune suppressive conditions ideal for tumor progression. Above immunomodulatory effects could enable cabozantinib to reverse the immunosuppressive phenotype in patients after failure with immune checkpoint inhibitors. The starting dose of cabozantinib of 60mg once daily in the current study is chosen in accordance with approved dose by FDA for treatment of advanced HCC

SBRT With Immunotherapy and Atezo-Bev in HCC With Major Portal Vein Thrombosis

Patients with PVTT involvement is a significant healthcare burden as they are present in up to 40% of patients with HCC at diagnosis. These patients exhibit a poorer prognosis compared to patients without PVTT, as a result they were often excluded from existing pivotal clinical trials \[9-11\]. Without management, the median OS in affected patients could be as short as 2 to 4 months. The role of liver-directed therapies is limited for patients with major PVTT. For example, percutaneous ablation to PVTT is technically challenging, especially for centrally located PVTT due to their proximity to hepatic vasculature and bile ducts. Transarterial therapies are contraindicated for patients with major PVTT due to risk of concurrent interruption of both hepatic arterial and portal venous blood flow resulting in severe liver ischemia. Therefore, patients with major PVTT are recommended to receive systemic treatment by international guidelines. Yet, the OS for patients with main PVTT remained poor. In the exploratory analysis of IMbrave-150, patients with main PVTT who received atezolizumab plus bevacizumab had a median OS of 7.6 months only, compared to 21.1 months for those without PVTT. There is a huge unmet for this group of patients with dismal prognosis. SBRT is a radiotherapy technique that enables delivery of high dose of radiation in an extremely precise manner. Compared to more conventional radiotherapy techniques such as intensity modulated radiotherapy (IMRT), SBRT has the advantage of superior disease control, minimizing dose to normal tissue and toxicity, and reduction of overall treatment time. For patients with PVTT, a number of retrospective and prospective trials have shown that SBRT can offer durable local control for patients with PVTT involvement. For instance, a randomized trial conducted in Korean which compared the combination of TACE-radiation (TACE-RT) with sorafenib, involving 90 patients with Child-Pugh A HCC with macrovascular invasion (MVI) (35% had main or bilateral portal vein involvement), showed improved 12-week PFS (86.7% vs. 34.3%), time-to-progression (31.0 vs. 11.7 weeks; p\<0.001), and OS (55.0 vs. 43.0 weeks; p=0.04) with TACE-RT. In a Canadian single-center retrospective study including 128 patients with HCC and MVI treated with SBRT between 2003 to 2016, 1-year local control was 87.4% and median OS was 18.3 months. Given the existing evidence, it would be of interest to study the efficacy and safety of atezolizumab plus bevacizumab and SBRT to portal venous tumour thrombosis in this patient group.

Durvalumab and Tremelimumab in Combination With Y-90 SIRT for Intermediate Stage HCC

A Phase II study of immunotherapy with Durvalumab (MEDI4736) and Tremelimumab in combination with Y-90 SIRT for intermediate stage HCC

A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 as a Single Agent and in Combination With Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors

This is a first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175 when administered as a single agent and in combination with atezolizumab or pembrolizumab in adult participants with locally advanced or metastatic solid tumors, including non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, colorectal cancer (CRC), urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.

REGULUS: MRI-guided Adaptive SABR for Liver Cancers

Single arm unblinded study of simulation-free MRI-guided SABR with adaptive replanning in one session for treatment of patients with liver cancers

Adjuvant Anti-PD-1 Therapy in Resected Hepatocellular Carcinoma

Early hepatocellular carcinoma (HCC) recurrence (driven by residual tumors) and late recurrence (driven by de novo tumors) exhibit distinct biological behaviors, suggesting differential therapeutic vulnerabilities. The beneficiaries of adjuvant PD-1 inhibitors (aPD-1) and their efficacy across these temporally divergent recurrence patterns remains unestablished.

TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol for Unresectable HCC With Cirrhotic Portal Hypertension

In China, the majority of hepatocellular carcinoma (HCC) cases stem from chronic hepatitis B virus (HBV) infection and subsequent cirrhosis, with patients often presenting at the decompensated stage complicated by clinically significant portal hypertension (CSPH). CSPH not only limits treatment options and worsens prognosis but also leads to the frequent exclusion of such patients from pivotal clinical trials, resulting in a lack of high-level evidence for their management. Carvedilol, a non-selective beta-blocker, is a first-line therapy for portal hypertension. Emerging evidence suggests that this drug class may also modulate the tumor microenvironment and enhance the efficacy of immune checkpoint inhibitors. To address this unmet need, this study aims to explore a novel quadruple-therapy strategy (TACE + tislelizumab + lenvatinib + carvedilol) for the treatment of unresectable HCC with concurrent cirrhotic portal hypertension. The rationale is twofold: while controlling portal hypertension and safeguarding treatment safety, carvedilol may also potentiate immunotherapy by modulating adrenergic signaling, thereby achieving dual benefits of "liver protection" and "anti-cancer" synergy. Utilizing an efficient Simon's two-stage design, this study will conduct a preliminary assessment of the regimen's efficacy and safety with minimal risk, providing essential data to inform future confirmatory research.

Predictive Value of Minimal Residual Disease for Postoperative Recurrence and Adjuvant PD-1 Inhibitor in HCC

Hepatocellular carcinoma (HCC) is a leading global cause of cancer-related mortality. While curative resection is pivotal, high postoperative recurrence rates remain a major challenge. Adjuvant immune checkpoint inhibitors (ICIs) show promise in improving outcomes, but biomarkers to identify patients who will benefit are lacking. Current clinicopathological risk factors for minimal residual disease (MRD) are suboptimal in sensitivity and specificity. Circulating tumor DNA (ctDNA) analysis, reflecting real-time tumor dynamics, offers a promising approach for MRD detection. This study focuses on the methylation status of GNB4 and Riplet-genes located within HCC-associated CpG islands-using a bespoke bisulfite-conversion and qPCR assay to sensitively detect methylated alleles, thereby enabling MRD monitoring. To clinically validate this approach, we will conduct a prospective, multicenter cohort study assessing the predictive value of serial \*GNB4/Riplet\* methylation testing for recurrence and adjuvant therapy benefit.

Preliminary Evaluation of Clinical Application of SPECT Imaging Targeting GPC3

This project will target patients with highly clinically suspected or histopathology diagnosed hepatocellular carcinoma (HCC) using targeted GPC3-specific imaging agents (e.g. , Iodine-131-aGPC3-Scfv) for integrated SPECTCT imaging, to evaluate the pharmacokinetics distribution of the targeted drug in patients with hepatocellular carcinoma (HCC) by low-dose integrated diagnosis and treatment (i.e. , Iodine-131-RRB- imaging, to determine the metabolism, safety and tolerability of the drug in vivo Secondary objective: to evaluate the targeting of GPC3-SPECIFIC imaging agents in patients with hepatocellular carcinoma to assess the feasibility of this targeted agent for future treatment.

Sintilimab Combined With Stereotactic Body Radiotherapy as Neoadjuvant Therapy for Resectable Hepatocellular

This study is a prospective, randomized controlled, phase II trial evaluating the efficacy and safety of neoadjuvant therapy with Sintilimab combined with SBRT in patients with resectable hepatocellular carcinoma. After meeting the inclusion and exclusion criteria and providing informed consent, eligible subjects will be randomly assigned to the experimental group or the control group: * Experimental Group: Subjects will receive Sintilimab 200 mg via intravenous infusion on day 1 of each 3-week cycle, for a total of two cycles. This will be combined with SBRT, administered as 8 Gy per fraction for 3 fractions on days 1, 3, and 5. Surgery will be performed 4-6 weeks after the last treatment, following the assessment of the patient's condition. Postoperative adjuvant therapy with Sintilimab monotherapy (200 mg Q3W) will be administered until disease recurrence, death, intolerable toxicity, withdrawal of informed consent, initiation of new antitumor therapy, or other protocol-specified reasons occur, for a maximum of one year. * Control Group:Subjects will undergo surgery directly. Postoperative adjuvant therapy with Sintilimab monotherapy (200 mg Q3W) will be administered until disease recurrence, death, intolerable toxicity, withdrawal of informed consent, initiation of new antitumor therapy, or other protocol-specified reasons occur, for a maximum of one year.

TACE Versus HAIC, Combined With PD-1 Inhibitors and Lenvatinib for Unresectable Hepatocellular Carcinoma

Although the combination of transarterial chemoembolization (TACE) with PD-1 inhibitor plus lenvatinib has become a new standard, the therapeutic efficacy for unresectable hepatocellular carcinoma (uHCC) still requires improvement, as TACE remains limited for patients with multifocal lesions, hypovascular tumors, or those complicated with portal vein tumor thrombosis (PVTT). Hepatic arterial infusion chemotherapy (HAIC), as an alternative locoregional therapy, has demonstrated advantages in treating these refractory cases. Therefore, this study innovatively designs a prospective cohort study to conduct a comparison of the two triple-combination regimens-"HAIC plus PD-1 inhibitor and lenvatinib" versus "TACE plus PD-1 inhibitor and lenvatinib"-in terms of real-world efficacy and safety, with a focus on enrolling patients who are likely to have suboptimal responses to TACE. This research aims to provide high-level evidence for selecting the optimal combined locoregional strategy for uHCC patients, thereby directly guiding clinical practice and potentially advancing the optimization of treatment strategies and personalized precision medicine to improve patient survival outcomes.

A Study of Yttrium [90Y] Microsphere Injection in Combination With Targeted Immunotherapy in the Treatment of HCC

This study is A Randomized, Active-Controlled, Open-Label National Multicenter Phase 2 Registration Clinical Study of Yttrium \[90Y\] Microsphere Injection in Combination with Camrelizumab and/or Apatinib and Yttrium \[90Y\] Microsphere Injection Alone versus Conventional Transcatheter Arterial Chemoembolization (cTACE) in the Treatment of Unresectable or Non-Ablative, Non-Metastatic Hepatocellular Carcinoma (HCC). Its aim is to evaluate the efficacy and safety of yttrium \[90Y\] resin microsphere injection combined with Camrelizumab and/or apatinib compared with yttrium \[90Y\] resin microsphere injection alone in the treatment of inoperable or ablatable, non-metastatic HCC.

IL1RAP-targeting Chimeric Antigen Receptor T Cells in the Treatment of Relapsed/Refractory Hepatocellular Carcinoma

A Phase 1 Study of IL1RAP-targeting Chimeric Antigen Receptor T cells in the Treatment of Relapsed/Refractory Hepatocellular Carcinoma

Efficacy and Safety of Pracytarabine Versus Regorafenib in the Treatment of Patients With Hepatocellular Carcinoma

This is a Phase 2/3 study evaluating the efficacy and safety of Pracytarabine versus regorafenib in patients with advanced hepatocellular carcinoma (HCC) who have experienced treatment failure with standard systemic therapies involving targeted drugs and immune checkpoint inhibitors, or dual immune checkpoint inhibitors.

HOPE Against Cancer Recurrence in HCC

Liver transplantation is often performed to treat liver cancer, or hepatocellular carcinoma (HCC), in patients with impaired liver function due to cirrhosis. A shortcoming, however, is tumor recurrence after transplantation. Approximately 15 % of patients receiving livers develop recurrence and this depends on the quality of the liver received. Machine liver perfusion, for example, hypothermic oxygenated liver perfusion (HOPE), which means that the organ is perfused with an oxygen-rich fluid in a cold environment before transplantation, is a novel method to improve the quality of livers before implantation. The standard of care is cold storage without perfusion. The objective of this study is to compare the survival after tumor recurrence of patients after liver transplantation for HCC between perfused and not perfused livers. This study's hypothesis is that survival without tumor recurrence is improved when the liver is perfused before implantation. The study involves transplant centers worldwide, and adults with HCC waiting for liver transplantation are included. 220 Patients will be recruited within 12 months and then observed for at least 2 years after transplantation. To provide the most valid results, the patients will be randomly allocated to either the organ perfusion group or a control group with standard-of-care cold storage of the organ.

Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

It has been estimated that alcohol causes around 40% of premature liver deaths in Europe each year, although this number is probably underestimated. Alcohol-related liver disease (ALD) is the most common cause of liver cirrhosis and liver death in Europe with a peak age of deaths occurring among individuals aged 40 to 50. Despite these findings, ALD is little studied with only 5% of all clinical trials in the field of liver disease recorded on ClinicalTrials.gov and only 5% of all publications in the same research area. Liver cancer is the second most common cause of cancer-related death (15-20% survival at 5 years) and the second most common cause of alcohol-related cancers worldwide. Like other complex diseases, ALD-HCC results from the interaction between environmental determinants and genetic variations but knowledge of gene-environment interactions is currently lacking in this area. The GENIAL project will address these needs through a comprehensive evaluation of gene-environment interactions concerning ALD-HCC.

Evaluation of Risk of hEpatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the second cause of cancer-related mortality worldwide. Nonalcoholic fatty liver disease (NAFLD), that is hepatic accumulation of fat in excess of 5% not explained by at risk alcohol intake, is projected to become the leading cause of HCC in Western countries within 2025.NAFLD is most frequently caused by insulin resistance due to unhealthy lifestyle. Due to the epidemics of obesity and type 2 diabetes, NAFLD now affects one in three individuals worldwide. NAFLD-HCC frequently develops without overt cirrhosis suggesting that steatosis directly promotes hepatic carcinogenesis.

Y-90 Treatment Response Using Transarterial Radioembolization

This prospective clinical study will examine the ability of contrast-enhanced ultrasound (CEUS) to assess the treatment response of hepatocellular carcinoma (HCC) to transarterial radioembolization (TARE). HCC is the third leading cause of cancer mortality worldwide and the single fastest growing cause of cancer mortality in the United States. TARE is recommended for 15-25% of HCC patients. Treatment response is generally evaluated using contrast-enhanced Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) 1-2 months and 4-6 months post-TARE. Although TARE is an effective therapy, assessment of treatment response using CT/MRI is challenging because CT/MRI frequently diagnoses tumor response as equivocal or non-progressing for up to 6 months post-TARE based on Liver Imaging Reporting and Data System (LI-RADS) criteria. This delay in diagnosing tumor viability subsequently delays needed retreatment and can even serve as a barrier to transplantation. Our prior work in HCC locoregional therapy has shown CEUS provides improved sensitivity in detecting viable tumor following transarterial chemoembolization relative to traditional CT/MRI. Therefore, the investigators propose to evaluate both qualitative and quantitative CEUS as a tool for evaluating HCC post-TARE at similar time points of clinically recommended cross-sectional imaging, while also investigating the role of Kupffer phase imaging. The investigator plans to enroll a total of 30 patients scheduled for TARE of a treatment naïve HCC over an 18-month period, allowing for a minimum of 6 months follow up. Patients will undergo a CEUS examination within two weeks of their first two clinically indicated CT/MRI exams (obtained at Jefferson 1-2 months and 4-6 months post TARE). Patients will be recruited across six major hospitals within the Jefferson Health Enterprise. Those eligible for participation will be identified by project co-investigators and contacted by the study coordinator to discuss participation and to explain the study. The patient will be given time to consider the risks and benefits of the study and ask questions about participation. If agreeable, the patient will then arrange with the project coordinator to come to Jefferson's center city campus to sign consent and take part in the research study.

Effect of the HCC Liver-Link Intervention

This study is a pilot, multi-center randomized controlled trial testing the HCC Liver-Link intervention, a culturally tailored, multi-level program designed to reduce racial disparities in hepatocellular carcinoma (HCC) care. The intervention combines: (1) patient education to improve HCC-related disease and treatment knowledge, (2) social needs and substance use screening with referral to social work and community resources, and (3) facilitated access to subspecialty cancer care through a multidisciplinary HCC tumor board. A total of 40 Black patients with Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or downstaged B disease will be randomized to receive either the HCC Liver-Link intervention or usual care and followed for 6 months or until liver transplant waitlisting. Primary outcomes are time to receipt of curative therapies (liver transplantation or resection) and change in HCC-related knowledge. Findings will inform development of larger interventions to eliminate racial disparities in HCC outcomes.

Partial Immune-boost TACE in unrEseCTable HCC Patients Under Systemic Treatment

Study Objectives： Atezolizumab (anti-programmed death-ligand 1; anti-PD-L1) combined with bevacizumab (anti-vascular endothelial growth factor; anti-VEGF) or Durvalumab (anti-programmed death-ligand 1; anti-PD-L1) combined with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4; anti-CTLA4) have recently been established as a standard first-line systemic treatment for unresectable hepatocellular carcinoma (HCC). However, its objective response rate (ORR) is only less than 27% (1, 2), and the majority of patients died of HCC progression and liver failure. Therefore, there is an urgent need to develop a novel combination treatment strategy to overcome resistance to immunotherapy and improve patient outcomes. Transarterial chemoembolization (TACE) remains the standard treatment for patients with intermediate-stage hepatocellular carcinoma (HCC) (3, 4). However, in our previous retrospective study (5-7), the investigators consistently observed that this combination not only improves therapeutic responses but also significantly prolongs patient survival. The tumor necrosis caused by TACE may enhance the efficacy of systemic therapies by promoting the release of neoantigens, thereby stimulating immune responses (8-14). This concept has been substantiated in two recent trials involving intermediate-stage HCC (15, 16), where the addition of immune checkpoint inhibitors to TACE resulted in improved clinical outcomes. Nevertheless, this promising approach has yet to replace the decades-old standard treatment protocols, underscoring the need for further proof-of-concept studies. Both immunotherapy (atezolizumab/bevacizumab or durvalumab/tremelimumab) and transarterial chemoembolization (TACE) are approved treatment modalities for unresectable hepatocellular carcinoma (HCC) by the U.S. and Taiwan Food and Drug Administration (FDA). This phase II non-randomized trial is designed to prospectively evaluate the therapeutic efficacy, safety, and immunological responses in patients with unresectable HCC treated with a combination of immunotherapy and TACE. A particular focus of this study is to explore the potential immune-boosting effects of TACE, including its ability to enhance antigen presentation and stimulate anti-tumor immune responses.