Cryoablation + SD-101 for Liver Cancer

Overseen By Isabel Newton, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brain metastases, Cardiac impairment, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating advanced liver cancer. It combines cryoablation, a procedure using extreme cold to destroy cancer cells, with an experimental drug, SD-101. Participants will also receive two immune-boosting drugs, tremelimumab and durvalumab, to enhance the body's ability to fight cancer. The trial seeks individuals with advanced liver cancer who have not received prior systemic treatments and are not candidates for surgery. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using immunosuppressive medications, you must stop them 14 days before starting the trial, unless they are certain types of steroids or at low doses.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have tested SD-101 with immune therapies for various cancers. Research has shown that this combination is generally well-tolerated. For instance, when combined with another immune therapy, most patients experienced mild to moderate side effects, such as tiredness or fever. These side effects are common with cancer treatments and are usually not serious.

Additionally, SD-101 has been tested in various contexts, demonstrating safe use with other treatments. Major safety issues were not typically reported. Since this trial is in its early stages, the main goal is to ensure the treatment's safety. Testing SD-101 with cryoablation and the STRIDE regimen suggests confidence in its safety based on earlier research.

In this trial, patients will receive SD-101 with cryoablation and immune therapies (tremelimumab and durvalumab). Past data suggests this approach could be safe, but it remains important to monitor for any side effects with any new treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for liver cancer because it uniquely combines cryoablation with SD-101, followed by immune checkpoint inhibitors Tremelimumab and Durvalumab. Cryoablation directly targets and destroys cancer cells by freezing them, while SD-101 is infused to stimulate an immune response right at the tumor site. The subsequent use of Tremelimumab and Durvalumab further enhances the immune system's ability to attack cancer cells, offering a multi-pronged approach that differs from the standard chemotherapy or radiofrequency ablation treatments. This innovative combination aims to improve the body's natural defenses against liver cancer, potentially leading to more effective and lasting outcomes.

What evidence suggests that this trial's treatments could be effective for liver cancer?

In this trial, participants will receive a combination of treatments, including cryoablation and intrahepatic artery infusion of SD-101. Research has shown that SD-101, a type of medicine, might help the immune system fight liver cancer more effectively by activating certain immune cells and enhancing T cell response to cancer. Early studies suggest that SD-101 can improve the effectiveness of other cancer treatments, such as immune checkpoint inhibitors. Participants will also receive Tremelimumab and Durvalumab as part of the STRIDE treatment plan. These treatments have shown promise in boosting the body's immune response against cancer. Together, these treatments could offer a hopeful approach for treating advanced liver cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Adam Burgoyne, MD, PhD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with advanced liver cancer who are in good physical condition and haven't had previous systemic treatments for their cancer. They must have a tumor that's at least 3 cm away from sensitive areas, can't be candidates for local therapies like surgery or radiation, and should have acceptable liver function (Child-Pugh A or B7).

Inclusion Criteria

My liver cancer diagnosis follows international guidelines.

I am willing and able to sign a consent form for the study.

My cirrhosis diagnosis is confirmed clinically as per AASLD guidelines.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cryoablation and SD-101 Administration

Participants undergo ultrasound- and/or CT-guided cryoablation of a hepatic lesion and concurrent administration of SD-101

1 week

1 visit (in-person)

Treatment with STRIDE Regimen

Participants receive tremelimumab and durvalumab every 4 weeks

12 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Every 8 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Durvalumab
• SD-101
• Tremelimumab

Trial Overview The study tests the combination of cryoablation (freezing of the tumor) and SD-101 injected into the liver artery followed by immunotherapy drugs tremelimumab and durvalumab every four weeks to see if they're safe and effective against advanced hepatocellular carcinoma.

How Is the Trial Designed?

Group I: SD-101 Experimental Treatment 4 Interventions

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).

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

TriSalus Life Sciences

Collaborator

Trials

5

Recruited

70+

TriSalus Life Sciences, Inc.

Industry Sponsor

Trials

10

Recruited

420+

Published Research Related to This Trial

The study demonstrated that percutaneous cryoablation guided by CT is safe and feasible, as all seven pigs survived the procedure without complications or serious hemorrhage.

Cryoablation effectively created ice balls that corresponded well with areas of tissue necrosis, indicating that this method could be a reliable technique for targeting tumors in the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CT-monitored percutaneous cryoablation in a pig liver model: pilot study. Lee, FT., Chosy, SG., Littrup, PJ., et al.[2016]

Percutaneous cryoablation for liver metastases from breast cancer showed a high technical success rate of 92% and an effectiveness rate of 87.1% at one month after treatment, indicating it is a promising option for local tumor control.

The procedure was found to be safe, with no major complications reported, and it preserved quality of life in patients, as evidenced by stable symptoms and functioning scales at three months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation of liver metastases from breast cancer: initial experience in 17 patients. Zhang, W., Yu, H., Guo, Z., et al.[2015]

The new cryoprobe allows for effective percutaneous cryoablation of small liver tumors, with a study involving 15 patients showing no complications and stable liver function post-procedure.

Cryoablation was successful in achieving complete response in 6 cases and partial response in 5 cases, but the method is recommended primarily for tumors smaller than 3 cm due to limitations in the size of the ice ball created during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Percutaneous cryosurgery for liver tumors]. Nakazaki, H., Watanabe, M., Hasebe, Y., et al.[2006]

Percutaneous cryoablation of renal tumors smaller than 7 cm has a low overall complication rate of 8.3%, indicating it is a safe treatment option for patients.

Tumors larger than 4 cm are associated with a higher risk of major complications, highlighting the importance of tumor size in assessing treatment risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of percutaneous renal cryoablation: an international multicentre experience from the EuRECA retrospective percutaneous database. Garnon, J., Van Strijen, MJ., Nielsen, TK., et al.[2020]

Cryoablation (CA) is a safe and effective treatment for liver cancer located near critical structures, with a 100% technical success rate in 69 procedures performed on 66 patients, and no serious complications reported.

The cumulative local tumor progression rates were relatively low at 6 months (10.2%) and increased to 30.5% by 24 months, indicating that while some tumors may progress, CA effectively controls tumor growth in the short to medium term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous cryoablation for the treatment of liver cancer at special sites: an assessment of efficacy and safety. Ma, J., Wang, F., Zhang, W., et al.[2022]

Cryoablation is a promising treatment for unresectable liver cancers, such as hepatocellular carcinoma (HCC), as it can be performed using various methods (percutaneously, intraoperatively, and laparoscopically) and is relatively safe and efficient based on preliminary research.

This technique not only effectively induces tumor necrosis through iceball formation but also has minimal impact on surrounding blood vessels and can trigger a cryo-immunological response, making it a potential alternative treatment option when combined with other therapies like radiation and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Cryoablation for Liver Cancer. Niu, LZ., Li, JL., Xu, KC.[2022]

In a study of 143 patients undergoing liver tumor cryoablation, factors such as larger tumor size (≥4 cm), low pre-procedural platelet count (<100,000/μL), and prior local radiation therapy were identified as independent risk factors for reduced overall survival.

Interestingly, the occurrence of grade 3 or higher adverse events during the cryoablation procedure did not correlate with decreased survival, suggesting that the procedure itself may be safe in terms of long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Periprocedural factors associated with overall patient survival following percutaneous image-guided liver tumor cryoablation. Daye, D., Hu, EY., Glazer, DI., et al.[2022]

In a study of 78 patients with unresectable hepatocellular carcinoma (HCC), the combination of cryoablation and sorafenib showed promising efficacy, with a median overall survival of 12.2 months and a median time to progression of 6.6 months.

The treatment was well-tolerated, with 43.6% of patients achieving stable disease and 11.5% showing partial responses, indicating that this combination therapy is a viable option for patients with advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sorafenib combined with cryoablation to treat unresectable hepatocellular carcinoma. Ni, H., Yang, M., Guo, Z., et al.[2021]

Cryoablation is a safe and effective treatment for primary and metastatic liver tumors, particularly for patients at higher risk for major surgery, such as older adults or those with pre-existing liver conditions, as demonstrated in a study of 28 patients with 39 tumors.

Despite its safety, cryoablation has a high recurrence rate at the treated site (19%), indicating that while it can be a palliative option, it may not provide long-term disease-free survival, and careful patient selection is crucial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Realistic expectations for cryoablation of liver tumors. Helling, TS.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05220722

NCT05220722 | Pressure Enabled Delivery of SD-101 With ... This is an Open-label, Phase 1b/2 Study of the Pressure-Enabled Hepatic Artery Infusion (HAI) of SD-101, a TLR9 agonist, Alone or in Combination with ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2622

PERIO-02: Phase 1b pressure enabled regional immuno- ... Background: Immunotherapy (ICI) has shown limited survival benefit in patients (pts) with advanced HCC and intrahepatic cholangiocarcinoma ...

3. investors.trisaluslifesci.com investors.trisaluslifesci.com/news-releases/news-release-details/trisalus-life-sciences-presents-data-sd-101-delivered-trisalus

TriSalus Life Sciences Presents Data for SD-101 Delivered ... SD-101, the Company's investigational immunotherapeutic candidate, is designed to improve patient outcomes by treating the immunosuppressive ...

4. onclive.com onclive.com/view/research-collaboration-aims-to-bring-tlr9-agonist-sd-101-to-patients-with-pancreatic-and-liver-cancer

Research Collaboration Aims to Bring TLR9 Agonist SD ... Notably, these data suggest that SD-101 can stimulate innate immune cells and favorably program T cells to enhance responses to checkpoint ...

5. ccanewsonline.com ccanewsonline.com/issues/2024/september-2024-vol-5-no-3/3114:phase-1b-study-of-nelitolimod-sd-101-administered

Phase 1b Study of Nelitolimod (SD-101) Administered ... Real-world data from US veterans confirm the safety and efficacy of ivosidenib in treating IDH1-mutated cholangiocarcinoma, offering hope for improved outcomes ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9365346/

Intralesional SD-101 in Combination with Pembrolizumab ... Combined positive score was ≥1 to < 20 in 35 patients (70%) and ≥ 20 in 15 patients (30%) of 50 patients with available data. There were 12 patients with grade ...

7. onclive.com onclive.com/view/sd-101-with-immune-checkpoint-inhibition-generates-positive-results-in-uveal-melanoma-liver-metastasis

SD-101 With Immune Checkpoint Inhibition Generates ... The results showed that treatment with 2 mg of SD-101 plus nivolumab (Opdivo) led to a median progression-free survival (PFS) of 11.7 months and ...