Clinical Research Directory

A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors

This study is to evaluate the safety and tolerability to determine (i) the recommended Phase 2 dose (RP2D) of VMD-102 (Phase 1), and (ii) preliminary anti-tumor efficacy (Phase 2), in participants with advanced HCC, metastatic uveal melanoma (MUM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). The pharmacokinetics (PK), preliminary anti-tumor activity, and potential biomarkers of VMD-102 will also be assessed. VMD-102 will be the first selective PKC epsilon (PKCε or PKCe) kinase inhibitor to enter human clinical testing. Preclinical VMD-102 anti-tumor activities in mouse liver/HCC tumor models and preclinical toxicology and pharmacology studies support this study.

FAST (Focused Abbreviated Screening Technique)-MRI Study

The purpose of this study is to compare the diagnostic value of a reconstructed abbreviated Magnetic Resonance Imaging (MRI) from a full clinical exam, compared to ultrasound (US) for screening of liver cancer. Blood markers will be evaluated to determine their correlation to imaging. This study will help to determine whether abbreviated MRI is superior to ultrasound for diagnosis of liver cancer.

DNP-MRSI of HCC Metabolism to Predict Therapeutic Response

This proposal describes a non-therapeutic diagnostic clinical trial to estimate the ability of DNP-MRS imaging of hyperpolarized 1-13C-pyruvate uptake and metabolism to predict response following LRT with TACE/TARE/Microwave Ablation or ST in patients with Barcelona Clinic Liver Cancer (BCLC) stage A, B or C HCC. The primary hypothesis is that intratumoral pyruvate, lactate, alanine and carbon dioxide/bicarbonate measured by DNP-MRSI correspond to cellular viability resulting from recurrent or progressive HCC following LRT or ST. The secondary hypothesis is that lactate-to-alanine ratios measured by DNP-MRSI can distinguish well- vs. poorly perfused tumor regions as identified on contrast-enhanced MR imaging.

A Post Approval Study to Evaluate Safety and Effectiveness of Multicompartmental Dosimetry Planning.

The purpose of this study is to assess the safety and effectiveness of treating a tumor using a different planning method called MCD for the FDA-Approved device, TheraSphere. TheraSphere Microspheres are microscopic radioactive glass spheres that deliver radiation therapy in the liver tissue where they are placed. This study investigates a procedure called multicompartment dosimetry (MCD). When using a multicompartment dosimetry approach, the doctor will look at images of the liver to see where there is tumor to determine where to treat. That area will be divided into "compartments" where the dose to tumor and the healthy liver are calculated separately. The goal of MCD is to give the tumor a higher radiation dose while protecting more of the healthy part of the liver. Traditional planning for the TheraSphere Microspheres procedure uses single compartment dosimetry (SCD) which treats the tumor and the healthy liver as one area so the dose is more evenly distributed and the dose to the tumor may be lower than with the MCD approach. The single compartment approach is standard and is well established however this research study is to see if giving TheraSphere Microspheres with an MCD planning method is safe and effective by evaluating the effect of radiation on the liver as well as how the tumor responds to higher doses

Immune-Related Adverse Events and Clinical Outcomes of First-Line Immunotherapy in Egyptian Patients With Unresectable Hepatocellular Carcinoma

The goal of this observational study is to evaluate how well first-line immunotherapy works and investigate its association with immune-related adverse events (irAEs) in Egyptian adults with unresectable hepatocellular carcinoma (HCC), a type of liver cancer that cannot be removed by surgery. The main questions this study aims to answer are: * Are immune-related adverse events (irAEs), which are side effects caused by activation of the immune system, associated with treatment response and survival? * How effective and safe is first-line immunotherapy in Egyptian patients with unresectable HCC? The study will also explore whether routine blood markers, including eosinophil counts and markers of inflammation and nutritional status, are associated with treatment outcomes and the development of immune-related side effects. Changes in liver function and patients' health-related quality of life will also be evaluated. Approximately 294 patients receiving first-line immunotherapy as part of their routine medical care will be included. Patients may receive atezolizumab plus bevacizumab or durvalumab plus tremelimumab, as prescribed by their treating physicians. Researchers will not assign treatments or change patients' medical care. The study will include a review of existing medical records and prospective follow-up of eligible patients. Researchers will: * Review medical records to collect information about treatment, routine blood tests, imaging results, side effects, and clinical outcomes. * Follow eligible patients during routine medical visits to assess treatment response, survival, adverse events, and changes in liver function. * Ask prospectively enrolled participants to complete questionnaires about their health-related quality of life during scheduled follow-up assessments. Researchers will compare treatment outcomes between patients who develop irAEs and those who do not, while taking into account when these side effects occur.

Long-Term Extension Study for Participants Previously Enrolled in an Exelixis-Sponsored Study

The primary objective of this long-term extension study is to allow continued access to study treatment for eligible participants who are deriving clinical benefit in an Exelixis-sponsored study who do not have access to treatment locally.

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

A Phase 1/1B Study of ST-01156 in Patients with Advanced Solid Malignancies

Personalized Adaptive Radiotherapy for Hepatocellular Carcinoma

This study evaluates whether Personalized Ultrafractionated Stereotactic Adaptive Radiation Therapy (PULSAR) improves overall survival compared with best supportive care (BSC). The main questions this study aims to answer are: Does PULSAR improve overall survival compared with BSC? Does PULSAR delay deterioration in patient-reported outcomes and quality of life compared with BSC? Can adaptive radiotherapy delivered in ultrafractionated pulses improve the therapeutic ratio in patients with HCC and poor liver function? The study will compare PULSAR with BSC to evaluate differences in survival, disease control, liver function, and treatment-related toxicity. Participants randomized to the PULSAR arm will receive 24 Gy of radiation delivered in 3 fractions of 8 Gy each, administered every 3 weeks using adaptive stereotactic radiotherapy. Participants in the BSC arm will receive standard supportive care. All participants will undergo regular assessments of survival, disease progression, liver function, toxicities, and quality of life.

A Phase 1 Study of the Safety and Tolerability of CTX-10726

This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.

A Study to Evaluate the Safety and Tolerability of Pumitamig Alone or In Combination With Ipilimumab in Participants With First-Line Advanced or Unresectable Hepatocellular Carcinoma (HCC) (ROSETTA HCC-206)

The purpose of this study is to evaluate the safety and tolerability of Pumitamig alone or in combination with Ipilimumab in participants with first-line advanced or unresectable Hepatocellular Carcinoma (HCC)

Interventional Radiology Liver Directed Therapies and Hypofractionated Image-Guided Radiation Therapy in Veteran and Non-Veteran, Non-surgical Hepatocellular Carcinoma Patients

This is a research study to evaluate change in Quality of Life, as defined by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC C-30), from baseline to 1 month post treatment in two patient cohorts receiving Interventional Radiology Liver Directed Therapies or Hypofractionated Image-Guided Radiation Therapy.

Breath Research Narrow Validation for Gastrointestinal Cancer Detection

The investigators of this study are developing a simple breath test to help detect gastrointestinal (gut) cancers earlier, including cancers of the oesophagus (food pipe), stomach, pancreas, liver and bowel. These cancers often cause non-specific symptoms that are similar to benign conditions, making early diagnosis difficult. Delays between the onset of symptoms and referral for a diagnostic test such as an endoscopy or a scan, can allow the cancer to progress. The breath test detects small molecules called volatile organic compounds (VOCs) that are released in exhaled breath. Some of these VOCs are strongly associated with these cancers and may help identify high-risk patients who require urgent investigation. In practice, patients who come to their GP with concerning symptoms will be offered the breath test. If the test is positive, patients can be referred promptly for a diagnostic test, while those with a negative result can be reassured and offered re-testing if symptoms persist. Earlier diagnosis could improve access to curative treatment while reducing unnecessary invasive investigations. Previous studies have identified a panel of VOCs that appear to distinguish patients with gastrointestinal cancers from those without cancer. This study aims to confirm these findings in a new group of participants to determine whether the same biomarkers can be reliably identified. Participants will provide a breath sample, usually before a hospital procedure they are already scheduled to undergo, and complete a short questionnaire about their medical history and medications. Some participants will also be asked to drink a nutritional supplement before providing a second breath sample. The results will help determine whether the breath test is reliable enough for further clinical evaluation

PULSAR Radiotherapy Combined With Immunotherapy for High-Risk Advanced Liver Cancer

The goal of this clinical trial is to learn if adding PULSAR, a personalized adaptive stereotactic radiotherapy, to standard immunotherapy can control cancer longer in adults with high-risk advanced hepatocellular carcinoma (liver cancer). It will also learn about the safety of this combination. The main questions it aims to answer are: * What percentage of participants are alive without cancer progression 12 months after starting PULSAR? * What medical problems do participants have after PULSAR with immunotherapy? There is no comparison group. Results will be compared with published results of immunotherapy alone. Participants will: * Continue their usual immunotherapy * Receive 2 to 3 PULSAR sessions, 3 to 4 weeks apart, with the plan adjusted before each session * Give blood samples and fill out symptom questionnaires * Have checkups and scans for up to 3 years

A Study to Assess the Adverse Events and How Intravenously Infused Livmoniplimab in Combination With Budigalimab Moves Through the Bodies of Adult Chinese Participants With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) is a common cancer worldwide and a leading cause of cancer-related death. The majority of participants first presenting with HCC have advanced unresectable or metastatic disease. The purpose of this study is to assess adverse events and how livmoniplimab in combination with budigalimab moves through the body in adult Chinese participants with Locally Advanced or metastatic Child-Pugh A Hepatocellular Carcinoma (HCC). Livmoniplimab is an investigational drug being developed for the treatment of HCC. There are 2 stages to this study. Stage 1 is a safety run-in. There are 2 treatment arms in stage 1 and participants will receive escalating doses of Livmoniplimab in combination with budigalimab (fixed dose). Stage 2 is dose expansion. There are 2 treatment arms in stage 2 and participants will receive Livmoniplimab in combination with budigalimab in multiple doses. Approximately 20 adult participants will be enrolled in the study across 15 sites in China. In part 1 (dose escalation), participants will be intravenously infused with escalating doses of livmoniplimab in combination with budigalimab every 3 weeks. In part 2 (dose expansion), participants will be intravenously infused with livmoniplimab in combination with budigalimab in multiple doses every 3 weeks. The estimated duration of the study is up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

68Ga-NYM207 PET/CT Imaging in Hepatocellular Carcinoma

This is a prospective, single-center, single-arm, phase I/II study designed to evaluate (1) the safety, tolerability, and imaging characteristics of 68Ga-NYM207 (Phase A), and (2) the diagnostic performance of 68Ga-NYM207 in detecting hepatocellular carcinoma (HCC) (Phase B). This study will provide critical insights into the performance of 68Ga-NYM207 PET/CT as a non-invasive imaging tool for the detection of HCC.

SBRT Combined With Iparomlimab and Tuvonralimab (QL1706) and Bevacizumab for Hepatocellular Carcinoma

SBRT combined with dual PD-1/CTLA-4 blockade (iparomlimab and tuvonralimab, QL1706) and bevacizumab may provide complementary local and systemic antitumor activity in hepatocellular carcinoma (HCC). This prospective, single-arm, single-center study evaluates the efficacy and safety of stereotactic body radiotherapy (SBRT) to all intra- and extrahepatic lesions combined with QL1706 (7.5 mg/kg intravenously on day 1 every 3 weeks) and bevacizumab (15 mg/kg intravenously on day 1 every 3 weeks) in patients with inoperable locally advanced or oligometastatic HCC (BCLC stage B or C). All lesions receive SBRT at 8 Gy in 3-5 fractions completed within 30 days; systemic therapy starts within 1 week before or after the start of radiotherapy and continues as maintenance for up to 2 years, until progression, death, or unacceptable toxicity. The primary endpoint is objective response rate per RECIST 1.1. Secondary endpoints include complete response, disease control rate, time to response, duration of response, local control, progression-free survival, time to progression, and overall survival per RECIST 1.1 and mRECIST, safety per CTCAE v6.0, and quality of life per EORTC QLQ-C30 and QLQ-HCC18. A total of 33 patients will be enrolled at Beijing Cancer Hospital.

Study of Tegavivint Plus Zanzalintinib in Patients With Advanced Hepatocellular Carcinoma

The goal of this clinical trial is to evaluate the combination of zanzalintinib (XL092) and tegavivint in advanced hepatocellular carcinoma (HCC) and Wnt pathway mutations who have progressed after at least one prior line of systemic therapy and are naïve (not previously treated with) standard of care tyrosine kinase inhibitors targeting vascular endothelial growth factor signaling.

Utilize Imaging to Assess Changes in Hepatocellular Carcinoma Perfusion as Potentiated by Intra-Arterial Nitroglycerin

This is a single-arm, open-label, single-center, first-in-human feasibility study evaluating parenchymal blood volume (PBV) imaging as a tool to dynamically assess perfusional changes in hepatocellular carcinoma (HCC) potentiated by intra-arterial administration of nitroglycerin.

Biomarkers Usefulness in the Screening of Hepatocellular Carcinoma in an European High-risk Cohort.

Longitudinal, prospective, observational, non-interventional study, to evaluate the performance of tumour biomarkers Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) and their combinations (GAAD and GALAD algorithms) in the screening of HCC.

Continuation of First-line Therapy With Radiotherapy Versus Early Switch to Second-line Therapy in Oligoprogressive HCC

This multicenter, prospective, randomized, controlled, open-label, two-arm Phase III clinical trial is designed to evaluate whether adding radiotherapy to oligoprogressive lesions while continuing first-line systemic therapy at the time of oligoprogression can effectively prolong progression-free survival compared to early switching to second-line systemic therapy in oligoprogressive hepatocellular carcinoma.

STRATHEP: AI-Driven Treatment Stratification for Advanced Hepatocellular Carcinoma

STRATHEP develops and validates a multimodal AI model to predict treatment response in advanced hepatocellular carcinoma. By integrating digital pathology and MRI radiomics, the project identifies patients likely to benefit from modern systemic therapies, using the RECIST 1.1 framework as the primary benchmark.

Phase 1 Trial of ACE723, A Dual-Payload Antibody Drug Conjugate, in Patients With Advanced HCC Who Have Failed or Progressed on Standard Systemic Therapy Containing ICIs

ACE723 is a dual-payload antibody drug conjugate targeting glypican-3 (GPC-3) that is under investigation for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC).

Study of Zanzalintinib in Combination With Immuno-Oncology or Other Agents in Participants With Solid Tumors

This is a multicenter Phase 1b, open label, dose-escalation and cohort-expansion study, evaluating the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity, and effect of biomarkers of zanzalintinib administered alone, and in combination with nivolumab (doublet), nivolumab + ipilimumab (triplet) and nivolumab + relatlimab (triplet) and in combination with docetaxel and prednisone in participants with advanced solid tumors. In addition, the study will evaluate the effect of multiple dose administration of zanzalintinib on the single-dose pharmacokinetics of sensitive CYP3A4, CYP2C9, CYP2C19, or CYP1A2 substrates in participants with advanced solid tumors. In the Expansion Stage, the safety and efficacy of zanzalintinib as monotherapy and in combination therapy will be further evaluated in tumor-specific Expansion Cohorts.

NK521 in the Treatment of Advanced Solid Tumors

Eligible subjects with advanced hepatocellular carcinoma and ovarian cancer will be divided into two treatment groups based on the volume of ascites. Group A consists of patients with mild ascites, who will receive NK521 via intravenous infusion. Group B includes patients with moderate to severe ascites, who will be treated with investigator-selected systemic regimens combined with intraperitoneal perfusion of NK521. Systemic and local medications will be administered in accordance with the treatment regimens of respective groups, and the safety of the study drug will be monitored. Preliminary anti-tumor efficacy will be assessed using the RECIST 1.1 criteria at Week 6 after the first infusion of NK521. Catheter placement and ascites drainage will be performed 3 days prior to the first intraperitoneal perfusion of NK521. After the initial intraperitoneal perfusion treatment, the therapeutic effect on ascites will be evaluated per the WHO criteria for ascites assessment.