Immunotherapy for Melanoma

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Antiretrovirals, Immunosuppressants

Disqualifiers: Pregnancy, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: 1

Duration: Up to 378 days

3 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses STI-3031, delivered directly into lymph nodes or vessels with a special device, to treat patients with a specific type of melanoma that has spread but not yet reached the nearest lymph node. The treatment works by boosting the immune system to attack cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive drugs for active autoimmune disease, you may need to stop or adjust those medications. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Intra-Lymphatic Injection using Sofusa DoseConnect Device, STI-3031, STI-3031, AP160 complex component for melanoma?

Research shows that local chemotherapy combined with immunotherapy can lead to a high response rate in melanoma, with 85% of patients responding to treatment in a clinical trial. Additionally, intralesional therapies, which involve injecting treatment directly into the tumor, have shown promise in producing durable local responses and potentially stimulating a broader immune response. ^{1 2 3 4 5}

Is the immunotherapy treatment for melanoma safe for humans?

The safety data for the immunotherapy treatment, including adoptive cell therapy with tumor-infiltrating lymphocytes (TILs), shows that no serious adverse effects were reported in studies, and the treatment was generally well-tolerated. However, immune checkpoint inhibitors, another type of immunotherapy, have been associated with serious skin-related side effects, so monitoring by healthcare professionals is recommended. ^{6 7 8 9 10}

How is the treatment Intra-Lymphatic Injection using Sofusa DoseConnect Device, STI-3031 different from other melanoma treatments?

This treatment is unique because it uses a special device to deliver the drug directly into the lymphatic system, which may enhance the immune response against melanoma while reducing side effects compared to traditional methods that circulate the drug throughout the entire body. ^{11 12 13 14 15}

Research Team

Anastasios Dimou, M.D.

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with in-transit melanoma confined to a limb, or metastatic melanoma of the lymph nodes accessible for treatment. Participants must have adequate organ function and agree to use contraception. Excluded are pregnant or nursing individuals, those planning pregnancy soon, patients with ITM beyond reachable areas by DoseConnect, severe allergies to monoclonal antibodies or related substances, uncontrolled diseases, and certain prior treatments.

Inclusion Criteria

I have a visible or non-visible tumor or lymph node that is at least 1.0 cm big.

I am willing to give tissue samples for research.

Rochester only: Willingness to provide mandatory blood specimens for correlative research

Exclusion Criteria

You have had serious allergic reactions to other drugs like the one being tested in the study, or to certain dyes and substances.

I am not on any experimental drugs for my cancer.

My melanoma has spread and I haven't received treatment for it.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive STI-3031 intra-lymphatically via the DoseConnect device over 1-8 hours once weekly for 6 weeks in cycle 1 and once every 2 weeks for 6 weeks in cycle 2. Treatment may continue for up to 9 cycles based on response.

Up to 378 days

Weekly visits for cycle 1, bi-weekly visits for cycle 2

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 2-4 weeks, 90 days, and every 3 months for up to 2 years.

Up to 2 years

Treatment Details

Interventions

• Intra-Lymphatic Injection using Sofusa DoseConnect Device
• STI-3031

Trial Overview The trial is testing STI-3031—an anti-PD-L1 monoclonal antibody—administered directly into lymphatics using Sofusa DoseConnect. It aims to find the safest dose while observing how well it helps the immune system fight cancer spread through lymph vessels from an original tumor site.

Participant Groups

Group I: Treatment (STI-3031) Experimental Treatment 2 Interventions

Patients receive STI-3031 intra-lymphatically via the DoseConnect device over 1-8 hours QW on days 1, 8, 15, 22, 29, and 36 of cycle 1, and Q2W on days 1, 15, and 29 of cycle 2. Treatment repeats every 42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR at the end of cycle 2 receive 1-2 additional cycles in the absence of disease progression or unacceptable toxicity. Patients with PR or SD at the end of cycle 2 continue treatment for a total of 9 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Intratumoral therapy for advanced melanoma allows for direct delivery of medications into tumors, potentially increasing local drug concentration and attracting immune cells, which may lead to fewer systemic side effects.

This review highlights that intratumoral therapies can act as in situ vaccines, offering the possibility of controlling disease both locally within the tumor and systemically throughout the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral therapies and in-situ vaccination for melanoma. Huppert, LA., Daud, AI.[2022]

A retrospective analysis of 21 patients with advanced cutaneous melanoma showed that nonselected autologous tumor-infiltrating lymphocytes (TILs) resulted in a high overall response rate of 67% and a complete response rate of 19%, indicating significant efficacy even in patients who had previously undergone PD-1 inhibition.

The treatment was found to be safe, with no treatment-related deaths and a median overall survival of 21.3 months, suggesting that TIL therapy could be a promising option for patients with limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. Pillai, M., Jiang, Y., Lorigan, PC., et al.[2022]

In a study of 10 patients with advanced melanoma treated with autologous tumor-infiltrating lymphocytes (TILs) and interleukin-2 (IL-2), no serious adverse effects were reported, indicating a favorable safety profile for this immunotherapy approach.

Among the patients, there were instances of complete and partial remission, with one patient surviving for 9 years post-treatment, suggesting potential long-term benefits; however, the presence of certain T cell types was associated with shorter overall survival, highlighting the need for further research into optimizing treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. Saint-Jean, M., Knol, AC., Volteau, C., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Robust Antitumor Responses Result from Local Chemotherapy and CTLA-4 Blockade. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The Role of Intralesional Therapies in Melanoma. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Intratumoral therapies and in-situ vaccination for melanoma. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A phase I multi-institutional study of systemic sorafenib in conjunction with regional melphalan for in-transit melanoma of the extremity. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Burden of disease predicts response to isolated limb infusion with melphalan and actinomycin D in melanoma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. [2022]

7. Egypt pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Dendritic cell vaccination for metastatic melanoma: a 14-year monoinstitutional experience. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System. [2020]

10. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial of Lipovaxin-MM, a novel dendritic cell-targeted liposomal vaccine for malignant melanoma. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy for malignant melanoma with a tumor cell vaccine. [2019]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Immunotherapy for the management of advanced melanoma: the next steps. [2017]

13. United States pubmed.ncbi.nlm.nih.gov

Active specific immunization in the treatment of patients with melanoma. [2013]

14. Australia pubmed.ncbi.nlm.nih.gov

Nanotopography-based lymphatic delivery for improved anti-tumor responses to checkpoint blockade immunotherapy. [2020]

15. Germany pubmed.ncbi.nlm.nih.gov

Armed antibodies for cancer treatment: a promising tool in a changing era. [2021]