Combining IV immunotherapy with liver-directed procedures to downstage hepatocellular carcinoma
Leveraging Immunotherapy For Tumor Downstaging to Milan Criteria in Patients With Hepatocellular Carcinoma
This tests whether giving IV immunotherapy (tremelimumab plus durvalumab) together with a liver-directed procedure (Y90, TACE, or RFA) can shrink or control hepatocellular carcinoma in adults with intermediate or advanced disease so more people may become eligible for liver transplant.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 41 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Cedars-Sinai Medical Center Academic / other |
| Drugs / interventions | Durvalumab, methotrexate, cyclophosphamide, immunotherapy, tremelimumab, chemotherapy, radiation |
| Locations | 1 site (Los Angeles, California) |
| Trial ID | NCT07489976 on ClinicalTrials.gov |
What this trial studies
This phase 2 interventional protocol gives a STRIDE immunotherapy regimen (tremelimumab 300 mg plus durvalumab 1500 mg IV, followed by durvalumab every ~4 weeks up to 12 cycles) combined with a liver-directed tumor procedure selected per patient (Y90, TACE, or RFA). Patients must have biopsy- or guideline-confirmed HCC with measurable disease and adequate liver function (Child-Pugh A or B7) and performance status (ECOG ≤2). The primary aims are to monitor safety and see if the combination can shrink or control tumors enough to downstage patients toward transplant eligibility. Patients are closely monitored for immune- and procedure-related adverse events and tumor response by mRECIST.
Who should consider this trial
Good fit: Adults (≥18) with intermediate or advanced HCC beyond UCSF criteria who have biopsy-confirmed, measurable disease (≥10 mm target lesion by mRECIST), Child-Pugh A or B7 liver function, ECOG ≤2, and life expectancy ≥12 months are the intended participants.
Not a fit: Patients with decompensated liver disease (Child-Pugh class worse than B7), ECOG >2, non-measurable disease, active contraindications to immunotherapy or locoregional procedures, or significant comorbidities are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, the combination could increase the number of patients who can be downstaged to become eligible for curative liver transplantation and improve tumor control.
How similar studies have performed: Checkpoint inhibitor combinations including the STRIDE regimen have shown clinical activity in HCC and combining immunotherapy with liver-directed therapies has produced promising signals, but using this combination specifically for downstaging remains investigational.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Age ≥ 18 at the time of signing the Informed Consent Form.
2. Beyond UCSF criteria HCC with diagnosis confirmed histologically/cytologically, radiologically, or clinically per AASLD criteria, with life expectancy of at least 12 months.
3. 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.
4. 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.
5. 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.
6. 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.
7. Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.
Exclusion Criteria:
* 1- Known fibrolamellar HCC, sarcomatoid HCC, other rare HCC variant, or mixed cholangiocarcinoma and HCC.
2- Extrahepatic spread with organ involvement other than liver. 3- Portal vein tumor thrombus (VP3-4) or any viable hepatic vein tumor thrombus at screening.
4- History of immune therapy exposure (and-PD-1, and PDL-1, and anti-CTLA-4) treatment.
5- Is pregnant or breastfeeding or expecting to conceive or impregnate someone during the study period.
6- 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.
7- Patient lacks interest or inadequate psychosocial support for organ transplantation.
8- 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.
9- 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.
10- 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.
11- 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.
12- 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.
13- Treatment with investigational therapy within 28 days prior to initiation of study treatment.
14- 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.
15- 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.
* Participants who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.
16- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment, within 5 months after the final dose of ICI.
17- Radiotherapy within 28 days, or abdominal/pelvic radiotherapy within 60 days, prior to initiation of study treatment.
18- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment; or abdominal surgery, abdominal interventions, or significant abdominal traumatic injury within 60 days prior to initiation of study treatment; anticipation of need for major surgical procedure during the course of the study; or non-recovery from side effects of any such procedure.
19- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the study drugs, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
Where this trial is running
Los Angeles, California
- Cedars Sinai — Los Angeles, California, United States (Recruiting)
Study contacts
- Study coordinator: Ju Dong Yang, MD
- Email: judong.yang@cshs.org
- Phone: 310-423-6000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.