IIT2025-03-YANG-LIFT-HCC

NCT07489976 | Recruiting Phase 2 FDA Drug

• 1 other identifier: STUDY00004540
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators are doing this study to learn if a combination of immunotherapy and a liver-directed tumor procedure can safely and effectively shrink or control liver cancer (hepatocellular carcinoma, HCC). The goal is to try to lower the stage of the cancer so that more patients may become eligible for a liver transplant. The investigators will also closely watch for side effects from the study treatments. Section 2 has more details.

Conditions

Hepato Cellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Proportion of participants downstaged from beyond UCSF criteria to within Milan criteria by radiographic assessment

  The primary outcome is the proportion of enrolled participants with hepatocellular carcinoma who are successfully downstaged from disease burden exceeding UCSF criteria at baseline to within Milan criteria within 12 months after initiation of STRIDE-based therapy and locoregional treatment. Downstaging status will be determined by follow-up contrast-enhanced CT or MRI using the study's predefined imaging assessment criteria.

  12 month

Secondary Outcomes (1)

• Proportion of participants downstaged from beyond UCSF criteria to within Milan criteria by radiographic assessment

  12 month

Study Arms (1)

Age ≥ 18 Patients with HCC beyond UCSF criteria, ECOG performance status ≤ 2, and Child-Pugh A or B7

EXPERIMENTAL

STRIDE Regimen (Tremelimumab 300 mg AND Durvalumab 1500 mg) combined with LRT (TACE, TARE, or RFA)

Drug: STRIDE Regimen (Tremelimumab 300 mg AND Durvalumab 1500 mg) combined with LRT (TACE, TARE, or RFA)

Interventions

STRIDE Regimen (Tremelimumab 300 mg AND Durvalumab 1500 mg) combined with LRT (TACE, TARE, or RFA) DRUG

• To assess the success rate of combining ICIs and LRT (as neoadjuvant treatment) in tumor downstaging to Milan Criteria within 12 months of baseline STRIDE treatment in patients with HCC exceeding the University of California San Francisco (UCSF) criteria.

Age ≥ 18 Patients with HCC beyond UCSF criteria, ECOG performance status ≤ 2, and Child-Pugh A or B7

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 at the time of signing the Informed Consent Form.
• Beyond UCSF criteria HCC with diagnosis confirmed histologically/cytologically, radiologically, or clinically per AASLD criteria, with life expectancy of at least 12 months.
• Histologically confirmed HCC via liver biopsy obtained within 3 months prior to initiation of study treatment as part of SOC. If no historical biopsy is available, a biopsy must be performed at screening for confirmation. Screening liver biopsy may be conducted as part of research activities if not performed per SOC practice.
• ECOG performance status ≤ 2 within 7 days prior to initiation of study treatment.
• Child-Pugh A or B7 (5 to 7 points) at screening and within 7 days prior to study treatment. D1 ECOG/CTP may not repeat if screening ECOG/CTP collected within 7 days prior to D1.
• HCC with Measurable disease by mRECIST (see Appendix 11.2) (at least one ≥10mm target lesion) that is not suitable for resection per standard clinical practice and beyond UCSF criteria (see section 11.5) confirmed with most recent imaging obtained within 3 months prior to screening.
• For subjects of childbearing potential (SOCBP), negative serum or urine pregnancy test and agreement to use adequate contraception or abstinence from the time of screening until 3 months following the last dose of Durvalumab.
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

You may not qualify if:

• Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC.
• Extrahepatic spread with organ involvement other than liver. 3- Portal vein tumor thrombus (VP3-4) or any viable hepatic vein tumor thrombus at screening.
• History of immune therapy exposure (and-PD-1, and PDL-1, and anti-CTLA-4) treatment.
• Is pregnant or breastfeeding or expecting to conceive or impregnate someone during the study period.
• Active or history of autoimmune diseases, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis.
• Patient lacks interest or inadequate psychosocial support for organ transplantation.
• Patients who have a known concurrent malignancy that is progressing or requires active treatment, who have not completely recovered from prior treatment, or who have a significant malignancy history that, in the opinion of the investigator, should preclude participation.
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
• Active tuberculosis (TB), as documented by a positive purified protein derivative (PPD) skin test or TB blood test and confirmed by a positive chest X-ray within 3 months prior to initiation of study treatment.
• Active co-infection with HBV and HCV. Participants with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV.
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia, or any active infection that, in the opinion of the investigator, could impact participant safety.
• Treatment with investigational therapy within 28 days prior to initiation of study treatment.
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment.
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible.

Sponsors & Collaborators

• Ju Dong Yang: lead

Study Sites (1)

Cedars Sinai

Los Angeles, California, 90048, United States

RECRUITING

MeSH Terms

Interventions

tremelimumab; durvalumab

Central Study Contacts

Ju Dong Yang, MD

CONTACT

310-423-6000; judong.yang@cshs.org

Manaf Alsudaney, MD

CONTACT

3109677454; manaf.alsudaney@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Medical Director, Liver Cancer Program

Study Record Dates

• First Submitted: March 17, 2026
• First Posted: March 24, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)