Hepatocellular CarcinomaPhase 1NCT06710223
Cryoablation and Arterial Infusion of SD-101 in Combination With Durvalumab and Tremelimumab
A Phase 1 study testing SD-101, Cryotherapy and Tremelimumab in people with Hepatocellular Carcinoma, run by University of California, San Diego at 1 site in United States.
Trial summary
The goal of this Phase 1b clinical trial is to evaluate the safety and efficacy of cryoablation and hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma. After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- SD-101, Cryotherapy and Tremelimumab
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2025to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent prior to performance of any study- specific procedures.
- Age ≥ 18 years.
- Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants:
- For cirrhotic participants with no histological confirmation of diagnosis, clinical confirmation is required per AASLD criteria.
- Pathological diagnoses of HCC will be made according to the International Working Party criteria.
- HCC with a component that measures at least 3 cm and that is located 1 cm or greater away from sensitive structures, including large blood vessels, large bile ducts, pericardium, diaphragm, gallbladder, stomach, and bowel.
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- Is not a candidate for local therapies alone, including liver transplantation, tumor ablation, transarterial embolization, radiation therapy, or resection.
- No prior systemic therapy for advanced or metastatic HCC.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- Evaluable target lesions as per Response Evaluation Criteria in Solid Tumors RECIST v1.1 or mRECIST.
- Child-Pugh A or Child-Pugh B7 liver function.
- Life expectancy of ≥ 12 weeks.
- Adequate bone marrow function defined as:
- Peripheral absolute neutrophil count ≥ 1000/mm^3
- Platelet count ≥ 50,000/ mm^3
- Hemoglobin ≥ 8.0 g/dL
- Adequate renal function defined as creatinine clearance ≥ 50 ml/min
- Adequate liver and pancreatic function defined as:
- Total bilirubin ≤ 2.0 x institution's upper limit of normal, and
- Alanine transaminase (ALT) or Aspartate transaminase (AST) ≤ 5 x institution's upper limit of normal, and
- Albumin ≥ 2 g/dL
- Adequate central nervous system function defined as:
- patients with seizure disorder may be enrolled if on anticonvulsants and seizures are well controlled.
- Systolic blood pressure <160 mm Hg.
- Patients with partners of childbearing potential must agree to use adequate contraception during participation in the study.
- Patients able to become pregnant are eligible to enter the study if they are either:
- Of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including: i. Has had a hysterectomy; or ii. Has had a bilateral oophorectomy, or iii. Has had a bilateral tubal ligation, or iv. Is post-menopausal (demonstrates total cessation of menses for greater than or equal to 1 year); OR
- Of childbearing potential, has a negative serum pregnancy test at screening, and agrees to one of the following contraceptives: i. An intrauterine device with a documented failure rate of less than 1% per year; ii. Vasectomized partner who is sterile prior to the subject's entry and is the sole sexual partner for that woman; iii. Complete abstinence from sexual intercourse for 14 days before exposure to investigational product, during the clinical trial, and for at least 14 days after the last dose of investigational product; iv. Double barrier contraception defined as condom with spermicidal jelly, foam, suppository, or film; OR diaphragm with spermicide; OR male condom and diaphragm.
Who cannot join
- Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.
- Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)].
- Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
- Presence of cardiac impairment defined as:
- prior history of cardiovascular disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions; OR
- history of myocardial infarction/active ischemic heart disease within one year of study entry; OR
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- uncontrolled dysrhythmias; OR
- poorly controlled angina
- Participation in a trial of an investigational agent within the prior 30 days
- Pregnant or breast-feeding.
- High volume peritoneal or pleural effusions requiring centesis more frequently than every 14 days.
- Poorly controlled or refractory (grade 3-4) hepatic encephalopathy.
- History of allogeneic stem cell or solid organ transplantation.
- Prior history of pneumonitis/interstitial lung disease.
- Receipt of live vaccine within 30 days.
- Active or prior documented autoimmune or inflammatory disorders (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, multiple sclerosis). The following are exceptions to this criterion:
- Vitiligo or alopecia.
- Autoimmune-related hypothyroidism stable on thyroid replacement therapy.
- Any chronic skin condition that does not require systemic therapy.
- Controlled type 1 diabetes mellitus who are on an insulin regimen.
- Celiac disease controlled by diet alone.
- Without active disease in the last 5 year.
- Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
- Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection).
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
- Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
- Any concurrent condition that, in the investigator's opinion, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
San Diego, California, 92093
About this study
Official title: A Phase Ib Study of Cryoablation and Pressure-enabled Hepatic Arterial Infusion of Class C Toll-like Receptor 9 Agonist SD-101 in Combination With Durvalumab and Tremelimumab in Patients With Advanced Hepatocellular Carcinoma
The goal of this Phase 1b clinical trial is to evaluate the safety and efficacy of cryoablation and hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma. After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).
Read the detailed description
This is a phase I, single site study to determine the safety, tolerability, and efficacy of cryoablation combined with hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma (HCC). After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).
SD-101 (also called nelitolimod) is a CpG oligodeoxynucleotide (CpG-ODN). More specifically, SD-101 is a bacterial DNA fragment that functions as a toll-like-receptor 9 (TLR9) agonist on myeloid-derived suppressor cells (MDSC), plasmacytoid dendritic cells (pDC), and other immune cells. TLR9 activation by SD-101 reprograms the tumor microenvironment (TME) and activates the immune system, rendering the tumor more susceptible to cancer immunotherapies, such as immune checkpoint inhibitors (ICI).
This study will administer SD-101 by pressure-enabled drug delivery (PEDD) directly into the hepatic artery during the tumor cryoablation procedure. This treatment will be followed by the STRIDE regimen, which consists of the administration of 2 immune checkpoint inhibitors: single dose of the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) antibody tremelimumab at 300 mg and once-monthly dose of the anti-Programmed Death-Ligand 1 (PDL1) antibody durvalumab at 1500 mg.
The hypothesis of this phase I study is that treatment with SD-101 will improve the efficacy of tremelimumab plus durvalumab by stimulating a robust systemic antitumoral immune response.
Patients with advanced HCC eligible for ICI treatment will be enrolled. Seven to ten days before the first ICI dose, participants will undergo ultrasound- and/or CT-guided cryoablation of part of a single hepatic lesion and concurrent administration of SD-101. US-guided liver biopsy will also be performed immediately prior to cryoablation as well as 30 days (plus or minus 7 days) afterwards. Participants will continue on ICI therapy infusions per the STRIDE regimen and tumor response will be evaluated by contrast-enhanced multiphase MRI or CT every 8 weeks (plus or minus 7 days) for 1 year. After the first year, tumor assessment will be conducted every 12 weeks (plus or minus 14 days).
- Conditions
- Hepatocellular Carcinoma
- Being tested
- SD-101, Cryotherapy, Tremelimumab, Durvalumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SD-101Drug
Also called nelitolimod
Toll-like receptor 9 (TLR9) agonist
CryotherapyDevice
Cryoablation of liver
TremelimumabDrug
Anti-CTLA4
DurvalumabDrug
Anti-PDL1
| Study group | Role | What they receive |
|---|---|---|
| SD-101 | Experimental | Participants will be treated with cryoablation and intrahepatic artery infusion of SD-101. This treatment will be followed by administration of the immune checkpoint inhibitors Tremelimumab and Durvalumab (STRIDE regimen). Tremelimumab 300mg will be given intravenously once, 7-10 days after cryoablation + SD-101. Durvalumab 1500mg will be given intravenously at the same time as Tremelimumab, and then every 28 days (on day 1 of every subsequent cycle). Receives: Drug: SD-101; Device: Cryotherapy; Drug: Tremelimumab; Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events
The primary endpoint is the number and frequency of adverse events related to cryoablation and hepatic artery infusion of SD-101 in combination with durvalumab and tremelimumab.
Adverse events (AEs) during the 6 months following Cryo+SD-101 will be recorded. The NCI CTCAE version 5.0 will be used to grade adverse events. Incidence of AEs will be summarized by event type, grade and body system. Particularly, the rates of infusion reactions, major bleeding, major infection, and grade 3 or above non-infection adverse events will be reported. The proportion of patients having each type of adverse event will be summarized along with a corresponding 90% confidence interval calculated using the exact method. The rate and 90% exact CI of subjects who experience serious adverse events will also be reported.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2024
- Study start3 Jan 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- TriSalus Life Sciences, Inc., Boston Scientific Corporation
- Responsible party
- Principal investigator, Adam Burgoyne, MD, PhD, University of California, San Diego
- Investigators
- Adam Burgoyne, MD, PhD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06710223
- Sponsor's protocol ID
- 810313
- Status last verified
- Jul 2026
- First submitted
- 25 Nov 2024
- Last updated
- 28 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study of Cryoablation and Pressure-enabled Hepatic Arterial Infusion of Class C Toll-like Receptor 9 Agonist SD-101 in Combination With Durvalumab and Tremelimumab in Patients With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT06710223
- Acronym / sponsor ID
- 810313
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- TriSalus Life Sciences, Inc., Boston Scientific Corporation
- Study start
- 3 Jan 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 29 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this Phase 1b clinical trial is to evaluate the safety and efficacy of cryoablation and hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma. After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).
Detailed description
This is a phase I, single site study to determine the safety, tolerability, and efficacy of cryoablation combined with hepatic arterial administration of SD-101 in participants with advanced hepatocellular carcinoma (HCC). After this procedure, participants will be treated with tremelimumab and durvalumab every 4 weeks (STRIDE regimen).
SD-101 (also called nelitolimod) is a CpG oligodeoxynucleotide (CpG-ODN). More specifically, SD-101 is a bacterial DNA fragment that functions as a toll-like-receptor 9 (TLR9) agonist on myeloid-derived suppressor cells (MDSC), plasmacytoid dendritic cells (pDC), and other immune cells. TLR9 activation by SD-101 reprograms the tumor microenvironment (TME) and activates the immune system, rendering the tumor more susceptible to cancer immunotherapies, such as immune checkpoint inhibitors (ICI).
This study will administer SD-101 by pressure-enabled drug delivery (PEDD) directly into the hepatic artery during the tumor cryoablation procedure. This treatment will be followed by the STRIDE regimen, which consists of the administration of 2 immune checkpoint inhibitors: single dose of the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) antibody tremelimumab at 300 mg and once-monthly dose of the anti-Programmed Death-Ligand 1 (PDL1) antibody durvalumab at 1500 mg.
The hypothesis of this phase I study is that treatment with SD-101 will improve the efficacy of tremelimumab plus durvalumab by stimulating a robust systemic antitumoral immune response.
Patients with advanced HCC eligible for ICI treatment will be enrolled. Seven to ten days before the first ICI dose, participants will undergo ultrasound- and/or CT-guided cryoablation of part of a single hepatic lesion and concurrent administration of SD-101. US-guided liver biopsy will also be performed immediately prior to cryoablation as well as 30 days (plus or minus 7 days) afterwards. Participants will continue on ICI therapy infusions per the STRIDE regimen and tumor response will be evaluated by contrast-enhanced multiphase MRI or CT every 8 weeks (plus or minus 7 days) for 1 year. After the first year, tumor assessment will be conducted every 12 weeks (plus or minus 14 days).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SD-101 | Experimental | Drug: SD-101, Device: Cryotherapy, Drug: Tremelimumab, Drug: DurvalumabParticipants will be treated with cryoablation and intrahepatic artery infusion of SD-101. This treatment will be followed by administration of the immune checkpoint inhibitors Tremelimumab and Durvalumab (STRIDE regimen). Tremelimumab 300mg will be given intravenously once, 7-10 days after cryoablation + SD-101. Durvalumab 1500mg will be given intravenously at the same time as Tremelimumab, and then every 28 days (on day 1 of every subsequent cycle). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Willing and able to provide written informed consent prior to performance of any study- specific procedures.
- Age ≥ 18 years.
- Locally advanced or metastatic and/or unresectable hepatocellular carcinoma (HCC) with diagnosis confirmed by histology/cytology or clinically by American Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic participants:
- HCC with a component that measures at least 3 cm and that is located 1 cm or greater away from sensitive structures, including large blood vessels, large bile ducts, pericardium, diaphragm, gallbladder, stomach, and bowel.
- Is not a candidate for local therapies alone, including liver transplantation, tumor ablation, transarterial embolization, radiation therapy, or resection.
Key exclusion criteria (27 listed)
- Brain metastases or spinal cord compression, unless treatment was completed at least 4 weeks before study entry, and stable without steroid treatment for at least 4 weeks.
- Evidence of severe or uncontrolled systemic diseases [e.g., unstable or uncompensated respiratory, cardiac (including life threatening arrhythmias)].
- Unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy except alopecia (if applicable) unless agreed that the patient can be entered after discussion with the Medical Monitor.
- Presence of cardiac impairment defined as:
- Participation in a trial of an investigational agent within the prior 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SD-101Also: nelitolimodToll-like receptor 9 (TLR9) agonist | Drug | SD-101 |
| CryotherapyCryoablation of liver | Device | SD-101 |
| TremelimumabAnti-CTLA4 | Drug | SD-101 |
| DurvalumabAnti-PDL1 | Drug | SD-101 |
Primary outcome
Adverse Events
Time frame: 6 months
The primary endpoint is the number and frequency of adverse events related to cryoablation and hepatic artery infusion of SD-101 in combination with durvalumab and tremelimumab. Adverse events (AEs) during the 6 months following Cryo+SD-101 will be recorded. The NCI CTCAE version 5.0 will be used to grade adverse events. Incidence of AEs will be summarized by event type, grade and body system. Particularly, the rates of infusion reactions, major bleeding, major infection, and grade 3 or above non-infection adverse events will be reported. The proportion of patients having each type of adverse event will be summarized along with a corresponding 90% confidence interval calculated using the exact method. The rate and 90% exact CI of subjects who experience serious adverse events will also be reported.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam Burgoyne, MD, PhD principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SD-101, Cryotherapy and Tremelimumab in people with Hepatocellular Carcinoma, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Events (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.