What is the mechanism of action of this treatment?

Common treatments for melanoma, such as Tumor Infiltrating Lymphocytes (TIL) therapy, checkpoint inhibitors (e.g., nivolumab, pembrolizumab), and interleukin-2 (IL-2) therapy, work by enhancing the body's immune response against cancer cells. TIL therapy involves extracting immune cells from the tumor, expanding them in the lab, and reinfusing them into the patient to attack the cancer. Checkpoint inhibitors block proteins that inhibit immune cells, thereby boosting the immune response. IL-2 therapy stimulates the growth and activity of immune cells. These mechanisms are vital for melanoma patients as they offer targeted, immune-based approaches that can lead to durable responses and potentially long-term remission.

What side effects are associated with this type of intervention?

Common treatments for melanoma, particularly immunotherapies like nivolumab, ipilimumab, and Tumor Infiltrating Lymphocytes (TIL) therapy, often result in immune-related adverse events (irAEs). These can include skin reactions, endocrine issues, and gastrointestinal problems. Severe side effects may involve infusion reactions, pneumonitis, and colitis. TIL therapy specifically may cause fever, fatigue, and itching, with most adverse events being mild to moderate.

What prior FDA approvals exist?

The FDA has approved several immunotherapies for the treatment of melanoma, particularly those targeting immune checkpoints. Notable approvals include pembrolizumab and nivolumab, both PD-1 inhibitors, which have shown significant efficacy in improving overall survival in metastatic melanoma. Additionally, the combination of nivolumab and ipilimumab, a CTLA-4 inhibitor, has been approved for its enhanced efficacy in certain patient populations. While TIL therapy, like TBio-4101, is still under investigation, these approved treatments share a common goal of harnessing the immune system to target and destroy melanoma cells.

What other types of research exist?

Promising novel alternatives to TBio-4101 for melanoma patients include: 1) Combination of nivolumab (PD-1 inhibitor) and ipilimumab (CTLA-4 inhibitor), which has shown improved response rates and disease control. 2) Relatlimab, a LAG-3 inhibitor, in combination with nivolumab, offering a favorable toxicity profile and improved progression-free survival. 3) Experimental CAR-T cell therapies and other immune checkpoint inhibitors like pembrolizumab (PD-1 inhibitor) and durvalumab (PD-L1 inhibitor) are also being explored in clinical trials.

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Cytokine

TBio-4101 + Chemo + IL-2 for Skin Cancer

Phase 1

Recruiting

Led By Amod Sarnaik, MD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

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

Must have

Participants must be willing and able to undergo an apheresis procedure

Participants must have ECOG performance status of 0 or 1

Must not have

Participants taking systemic steroid therapy (other than replacement therapy) or therapy with any immunosuppressive medications such as mycophenolate mofetil (MMF)

Participants with autoimmune disease currently or within the past 6 months requiring systemic treatment with immunosuppressive doses of corticosteroids

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at 6 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment that uses a patient's own immune cells, grown in a lab, to fight advanced melanoma that cannot be removed by surgery or has spread. The goal is to see if this approach is safe and effective. Using a patient's own immune cells to fight cancer has shown promise in treating advanced melanoma.

Who is the study for?

This trial is for adults aged 18-75 with unresectable or metastatic melanoma, including various types like cutaneous and ocular melanoma. Participants must have adequate organ function, an ECOG status of 0 or 1, and be willing to practice birth control. Those with treated brain metastases, a negative pregnancy test (if applicable), and the ability to sign consent can join. Excluded are pregnant women, those with severe heart issues or immunodeficiency disorders, active infections requiring IV antibiotics, history of severe allergies to study drugs, certain lung function impairments, autoimmune diseases needing steroids in the past 6 months.

What is being tested?

The trial tests TBio-4101 therapy using tumor infiltrating lymphocytes after lymphodepleting chemotherapy followed by interleukin-2 (IL-2) in participants with advanced melanoma. It aims to assess if this approach is feasible and safe while also evaluating its effectiveness against the cancer.

What are the potential side effects?

Potential side effects may include reactions from immune system activation such as fever and fatigue; effects from chemotherapy like nausea and low blood cell counts; risks associated with IL-2 treatment which could involve fluid retention and low blood pressure; plus site-specific reactions from TIL infusion.

Eligibility Criteria

Inclusion Criteria

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

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I am willing and able to undergo a procedure to collect my blood cells.

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I can carry out all my usual activities without help.

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I am between 18 and 75 years old.

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My organs and bone marrow are working well.

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I am a woman who can have children and my pregnancy test is negative.

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I have a tumor larger than 1 cm that can be surgically removed for TIL therapy.

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I have enough stored TIL cells for TBio-4101 therapy after a pre-REP.

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My melanoma cannot be removed by surgery and includes skin, mucosal, or eye melanoma.

Exclusion Criteria

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

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I am not on steroids or immunosuppressive medications.

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I have an autoimmune disease and have been on high-dose steroids in the last 6 months.

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My heart's pumping ability is reduced, or I have slight limitations on physical activity.

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My lung function tests show less than 60% of the expected values.

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I have previously undergone cell therapy.

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I am currently on IV antibiotics for an infection.

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My tumor is causing blockage, bleeding, or might soon break through an organ.

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I need ongoing blood thinner treatment that can't be stopped or switched to a specific type.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at 6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and at 6 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

Percentage of Participants that Successfully Receive TBio-4101

Secondary study objectives

12 Month Overall Survival (OS)

12 Month Progression Free Survival (PFS)

6 Month Overall Survival (OS)

+3 more

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: Infusion of TBio-4101 TILExperimental Treatment4 Interventions

TBio-4101 is a tumor-infiltrating lymphocyte (TIL) product: participants tumor tissue is surgically removed and immune T-cells are taken out of the tumor and multiplied, or grown, in the laboratory. TIL product infused intravenously over 20 to 30 minutes within 2 to 4 days after the last dose of fludarabine Participants will also receive: * Cyclophosphamide dose 60 mg/kg/day for 2 days administered IV in 250 mL dextrose 5% in water infused simultaneously with Mesna 15 mg/kg/day delivered over 1 hour per day for 2 days. Fludarabine 25 mg/m2/day is delivered by intravenous piggyback daily over 15-30 minutes for 5 days. * Interleukin-2 (IL-2)- will be given to participants through IV after they receive the infusion of the TIL. IL-2 is administered at a dose of 600,000 IU/kg (based on actual body weight) IV every 8-12 hours beginning within 24 hours of TIL infusion for a maximum of 6 doses.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Interleukin-2

1994

Completed Phase 3

~840

Fludarabine

2012

Completed Phase 4

~1860

Cyclophosphamide

2010

Completed Phase 4

~2310

0 / 16Eligibility 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 melanoma, such as Tumor Infiltrating Lymphocytes (TIL) therapy, checkpoint inhibitors (e.g., nivolumab, pembrolizumab), and interleukin-2 (IL-2) therapy, work by enhancing the body's immune response against cancer cells. TIL therapy involves extracting immune cells from the tumor, expanding them in the lab, and reinfusing them into the patient to attack the cancer. Checkpoint inhibitors block proteins that inhibit immune cells, thereby boosting the immune response. IL-2 therapy stimulates the growth and activity of immune cells. These mechanisms are vital for melanoma patients as they offer targeted, immune-based approaches that can lead to durable responses and potentially long-term remission.