What is the mechanism of action of this treatment?

Common treatments for Uveal Melanoma include immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) and targeted therapies (e.g., BRAF inhibitors like vemurafenib). Immune checkpoint inhibitors work by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. TLR 9 agonists like SD-101 activate the immune system by stimulating toll-like receptor 9, leading to an increased production of interferons and other cytokines that promote anti-tumor immunity. These mechanisms are crucial for Uveal Melanoma patients as they help to overcome the immune-evasive properties of the tumor, potentially improving treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for uveal melanoma include immune checkpoint inhibitors and other immunotherapies. These treatments can lead to a range of side effects. Immune checkpoint inhibitors, for example, are associated with ocular adverse events such as dry eye, conjunctivitis, and uveitis. Other side effects may include fatigue, skin rash, and gastrointestinal issues. The specific treatment being studied, SD-101, a TLR 9 agonist, when used in combination with checkpoint blockade, may also present similar immune-related side effects, although detailed side effect profiles for SD-101 specifically are not extensively documented.

What prior FDA approvals exist?

Currently, there are no FDA-approved TLR 9 agonists specifically for the treatment of uveal melanoma. However, treatments for metastatic uveal melanoma often include immune checkpoint inhibitors such as pembrolizumab and nivolumab, which target PD-1, and ipilimumab, which targets CTLA-4. These therapies aim to enhance the body's immune response against cancer cells. The study of SD-101, a TLR 9 agonist, in combination with checkpoint blockade represents an investigational approach to further stimulate the immune system to target uveal melanoma.

What other types of research exist?

Promising novel alternatives to SD-101 for Uveal Melanoma patients include checkpoint inhibitors such as pembrolizumab and nivolumab, which have shown efficacy in various cancers including melanoma. Additionally, combination therapies involving checkpoint inhibitors and other agents like bevacizumab are being explored. Another potential alternative is the use of TLR 7 and 8 antagonists like E6742, which have shown immunomodulatory effects in early studies.

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Checkpoint Inhibitor

SD-101 + Checkpoint Blockade for Metastatic Uveal Melanoma

Phase 1

Waitlist Available

Research Sponsored by TriSalus Life Sciences, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Has measurable disease in the liver according to RECIST v.1.1 criteria

Has adequate organ function at screening as evidenced by: Platelet count >100,000/μL, Hemoglobin ≥8.0 g/dL, White blood cell count (WBC) >2,000/μL, Serum creatinine ≤2.0 mg/dL unless the measured creatinine clearance is ≥30 mL/min calculated by Cockcroft-Gault formula, Total and direct bilirubin ≤2.0 × the upper limit of normal (ULN) and alkaline phosphatase ≤5 × ULN. For patients with documented Gilbert's disease, total bilirubin up to 3.0 mg/dL is allowed, ALT and AST ≤5 × ULN, Prothrombin time/International Normalized Ratio (INR) or activated partial thromboplastin time (aPTT) test results at screening ≤1.5 × ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose for at least 4 weeks prior to the first dose of study intervention)

Must not have

Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection

Has previously received SD-101

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 12 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for adults with eye cancer that has spread. The treatment uses a special drug to boost the immune system, either alone or with other immune-boosting drugs. It aims to help the body better fight the cancer.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at the infusion site, flu-like symptoms due to immune system activation by SD-101, fatigue, skin rash, digestive issues from checkpoint inhibitors like diarrhea and colitis; potential for autoimmune reactions where the body attacks its own cells; increased risk of infection.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver cancer can be measured by standard health scans.

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My blood tests show my organs are working well.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My cancer, mainly in the liver, has been confirmed by lab tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have an active hepatitis B or C infection.

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I have previously been treated with SD-101.

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I have brain metastasis that hasn't been treated.

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I am taking more than 10 mg of prednisone daily or other similar medications.

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I have severe liver issues, including blood clots in the liver vein or severe portal hypertension.

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My liver is mostly replaced by cancer in both lobes.

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I do not have COVID-19, severe infections, or uncontrolled HIV.

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I haven't had chemotherapy or experimental drugs in the last 14 days.

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I had bacterial pneumonia within the last 8 weeks.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 12 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Phase 1: To Determine the Maximum Tolerable Dose (MTD) or Optimal Dose of SD-101 alone, in Combination with Nivolumab, and in Combination with Both Nivolumab and Ipilimumab

Phase 1: To Determine the Safety of SD-101 Alone, in Combination with Nivolumab, and in Combination with Both Nivolumab and Ipilimumab

Phase 1b: To Assess Overall Response Rate (ORR)

+1 more

Secondary study objectives

Phase 1: Determination of Single vs. Dual-agent CPI in Phase 1b using CTCAE v5.0

Phase 1: Determination of Single vs. Dual-agent CPI in Phase 1b using RECIST v1.1

Phase 1b: Assess Preliminary Efficacy in Terms of RECIST v1.1 for Immune Based Therapeutics

+3 more

Side effects data

From 2017 Phase 1 & 2 trial • 9 Patients • NCT02254772

100%

Myalgia

100%

Arthralgia

100%

Headache

100%

Fatigue

56%

Fever

56%

Injection site reaction

44%

Chills

33%

Nasal Congestion

33%

Bruising

33%

Cough

33%

Rash

33%

Swelling

22%

Induration

22%

Bloating

11%

Neutropenia

11%

Anemia

11%

Back pain

11%

Diarrhea

11%

Dysphagia

11%

Anorexia

11%

Nausea

11%

Flu Like Symptoms

11%

Pancytopenia

11%

Sepsis

11%

Malaise

11%

Increased Creatinine

11%

Dyspnea

100%

80%

60%

40%

20%

Study treatment Arm

Treatment (SD-101 + Ipilimumab + Radiation)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: SD-101Experimental Treatment4 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

SD-101

2014

Completed Phase 2

~90

Nivolumab

2015

Completed Phase 3

~4010

Ipilimumab

2015

Completed Phase 3

~3070

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Uveal Melanoma include immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) and targeted therapies (e.g., BRAF inhibitors like vemurafenib). Immune checkpoint inhibitors work by blocking proteins that prevent the immune system from attacking cancer cells, thereby enhancing the body's immune response against the tumor. TLR 9 agonists like SD-101 activate the immune system by stimulating toll-like receptor 9, leading to an increased production of interferons and other cytokines that promote anti-tumor immunity. These mechanisms are crucial for Uveal Melanoma patients as they help to overcome the immune-evasive properties of the tumor, potentially improving treatment outcomes.

The potential role of sunitinib targeting melanomas.