SD-101 + Checkpoint Blockade for Metastatic Uveal Melanoma

No longer recruiting at 9 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: TriSalus Life Sciences, Inc.

Must not be taking: Chemotherapy, Immunosuppressants

Disqualifiers: Brain metastasis, Hepatitis, Autoimmune, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for metastatic uveal melanoma, a rare eye cancer that has spread, primarily to the liver. The study uses SD-101, a drug that may help the immune system fight cancer, alone or with other drugs that block cancer's ability to hide from the immune system, such as Ipilimumab (Yervoy) and Nivolumab (Opdivo). Participants should have uveal melanoma with liver-dominant disease and should not have recently undergone certain cancer treatments. 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.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy over 10 mg of prednisone daily or equivalent, and you must be able to temporarily stop chronic anticoagulation therapy.

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

Research has shown that SD-101, administered through the liver's main artery, was well tolerated in past studies, meaning most patients did not experience serious side effects. One study demonstrated positive effects on the immune system, indicating potential effectiveness.

The other drugs in the trial, ipilimumab and nivolumab, have FDA approval for other uses, suggesting reasonable safety. However, as with any treatment, some patients might experience side effects, so staying informed and discussing them with a doctor is important.

Overall, while this trial is in an early stage, the treatments have shown promise in terms of safety based on past research and existing approvals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SD-101 because it offers a unique approach to treating metastatic uveal melanoma. Unlike the standard immunotherapies like ipilimumab and nivolumab, which are administered intravenously, SD-101 is delivered directly into the liver through hepatic artery infusion, potentially enhancing its effectiveness in targeting liver metastases. This direct delivery method could improve the concentration of the drug in the tumor area, possibly leading to better outcomes. Additionally, SD-101 is designed to stimulate the immune system in a novel way, potentially increasing the body's ability to fight cancer cells more effectively than current treatments.

What evidence suggests that this trial's treatments could be effective for metastatic uveal melanoma?

Research has shown that SD-101, which participants in this trial will receive, offers promising results for treating advanced eye cancer known as metastatic uveal melanoma. In some studies, combining SD-101 with drugs like nivolumab helped patients control their cancer for an average of 11.7 months, suggesting that the treatment can slow the cancer's growth. One study found that 88% of patients did not experience cancer progression for at least a year, and 89% were still alive after a year. These findings suggest that this treatment could be effective, especially for those who have tried similar therapies before. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

Adults over 18 with metastatic uveal melanoma, who haven't had certain recent treatments or severe side effects from past immunotherapies. They should be in relatively good health (ECOG PS of 0-1), have a life expectancy over 3 months, and not be pregnant or breastfeeding. Participants must agree to use effective contraception and have adequate organ function. Those with significant liver disease, active infections like COVID-19, other serious illnesses, or known allergies to trial drugs are excluded.

Inclusion Criteria

Able to understand the study and provide written informed consent prior to any study procedures

My liver cancer can be measured by standard health scans.

My blood tests show my organs are working well.

Exclusion Criteria

I have an active hepatitis B or C infection.

I have previously been treated with SD-101.

I have severe liver disease, had a serious reaction to immunotherapy, can't stop blood thinners, or have a bleeding disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Sentinel Cohort

Patients receive 2 SD-101 infusions (2 weeks apart) with assessments for toxicity

4 weeks

2 visits (in-person)

Cohorts A-C and Phase 1b

Patients receive 2 cycles of SD-101 with escalating doses, alone or in combination with checkpoint inhibitors

6 weeks

6 visits (in-person)

Optional Cohort D

Exploration of combination CPI regimens with modified SD-101 dosing schedule

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• SD-101

Trial Overview The trial is testing SD-101 delivered directly into the liver using pressure (PERIO) alone or combined with intravenous checkpoint inhibitors Nivolumab and Ipilimumab or Nivolumab plus Relatlimab. It's an early-phase study to see how safe this approach is for treating liver-dominant metastatic uveal melanoma.

How Is the Trial Designed?

Group I: SD-101 Experimental Treatment 4 Interventions

3 weekly doses of SD-101 given via hepatic artery infusion over 2 cycles

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

TriSalus Life Sciences, Inc.

Lead Sponsor

Trials

10

Recruited

420+

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6719557/

SD-101 in Combination with Pembrolizumab in Advanced ... The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti-PD-1 therapy, the ORR ...

3. targetedonc.com targetedonc.com/view/sd-101-and-checkpoint-blockade-shows-early-favorable-outcomes-in-umlm

SD-101 and Checkpoint Blockade Shows Early Favorable ... Encouraging progression-free survival and ctDNA molecular response rates were seen with SD-101 delivered via pressure-enabled drug delivery plus intravenous ...

4. dailynews.ascopubs.org dailynews.ascopubs.org/do/targeting-hepatic-myeloid-derived-suppressor-cells-intrahepatic-sd-101-early-results

Targeting Hepatic Myeloid-Derived Suppressor Cells With ... Based on clinical outcomes and immune data, 2 mg of SD-101 plus nivolumab is the candidate optimal dose, with a median PFS of 11.7 months ...

5. oncologycompass.com oncologycompass.com/blog/post/sd-101-and-checkpoint-blockade-a-promising-duo-for-umlm-treatment

A promising duo for UMLM treatment - Oncology Compass The biological effects of SD-101 are best at the lowest dose tested, revealing tumor microenvironment reprogramming and inflammatory cell ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.2521

Safety and early biologic effects of phase 1 PERIO-01 trial ... HAI of SD-101 has been well tolerated and associated with encouraging immunologic activity. Evidence of biologic effects at the lower doses of SD-101 with ...

7. jitc.bmj.com jitc.bmj.com/content/11/Suppl_2/A1757

1534 Clinical activity of SD-101 with immune checkpoint ... Across dose levels, median PFS was highest in Cohort B (2 mg) at 11.7 months, and disease control rate of 86% (6/7 SD). Serious grade 3/4 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04935229

Study Details | NCT04935229 | Intrahepatic Delivery of SD ... The choice of single- or double-agent CPI therapy together with SD-101 for Phase 1b will consider safety data in addition to response rates from Cohorts B and C ...