What side effects are associated with this type of intervention?

Common treatments for skin conditions that involve immune modulation include topical immunotherapy agents like DPCP and SADBE, as well as systemic immunosuppressants like cyclosporine. Topical immunotherapy can cause local skin reactions such as dermatitis, itching, and redness. Systemic treatments like cyclosporine may lead to more severe side effects, including liver enzyme elevation, pancreatitis, bone marrow suppression, and increased risk of infections. These treatments aim to modulate the immune system to achieve therapeutic effects, but they come with a range of potential adverse effects that need to be carefully managed.

What prior FDA approvals exist?

FDA-approved treatments for skin conditions that involve immunotherapy include checkpoint inhibitors like pembrolizumab and nivolumab, which are used for melanoma. These drugs enhance the immune system's ability to fight cancer cells. Additionally, talimogene laherparepvec (T-VEC) is an oncolytic virus therapy approved for melanoma, which works by directly killing cancer cells and stimulating an immune response. While these treatments are not gene-modified immune cells like FH-MCVA2TCR, they similarly aim to boost the body's immune response to target and destroy cancer cells.

What other types of research exist?

Promising novel alternatives for treating skin conditions include: 1) Beremagene geperpavec (B-VEC), a modified herpes simplex virus 1 vector delivering the COL7A1 gene for dystrophic epidermolysis bullosa (DEB), which has shown significant wound healing. 2) Stem cell therapy, including allogeneic bone marrow transplantation and mesenchymal stem cells (MSCs), which have demonstrated improved wound healing and reduced blistering in epidermolysis bullosa. 3) Genetically modified autologous cultured skin grafts using a retroviral vector containing the nonmutated LAMB3 gene for junctional epidermolysis bullosa (JEB), which resulted in stable epidermal regeneration.

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CAR T-cell Therapy

Gene-Modified Immune Cells for Skin Cancer

Phase 1 & 2

Waitlist Available

Led By Joshua Veatch

Research Sponsored by Fred Hutchinson Cancer Research Center

Eligibility Criteria Checklist

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

Must have

HLA-A*02:01 positive

Metastatic or unresectable MCPyV-associated VP-MCC that has progressed on or after prior treatment with a PD-1 axis immune checkpoint inhibitor

Must not have

Untreated brain metastases

Active autoimmune disease requiring immunosuppressive therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 1 year post infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well lab-modified immune cells work in treating advanced Merkel cell cancer. The treatment aims to improve the body's ability to fight the cancer by enhancing the immune cells.

Who is the study for?

This trial is for adults with Merkel cell cancer that's spread or can't be surgically removed, who've had prior treatment with a PD-1 axis inhibitor but got worse without severe side effects. They must have specific blood and organ function levels, no active autoimmune diseases needing strong meds, no recent other cancer treatments, and not be on high-dose steroids.

What is being tested?

The study tests gene-modified immune cells (FH-MCVA2TCR) combined with drugs like Avelumab and Pembrolizumab to see if they're safe and effective against advanced Merkel cell cancer. It involves modifying patients' own immune cells in the lab to fight the cancer better.

What are the potential side effects?

Possible side effects include reactions related to the immune system being overly activated by the modified cells or drugs used in this trial. This could lead to inflammation in various organs, flu-like symptoms from Interferon Gamma-1b, infusion-related reactions, fatigue, or skin conditions.

Eligibility Criteria

Inclusion Criteria

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

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I am HLA-A*02:01 positive.

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My Merkel cell carcinoma has worsened despite treatment with a PD-1 inhibitor.

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I am 18 years old or older.

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I am 60 or older and my heart's pumping ability is at least 35%.

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I understand the study and can give my consent.

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I can care for myself but may need occasional help.

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My Merkel cell carcinoma cannot be removed by surgery.

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I was treated with a PD-1 inhibitor and my cancer progressed without severe side effects.

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My Merkel cell carcinoma is confirmed to be virus-positive.

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My cancer is MCPyV positive.

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I experience mild or no shortness of breath.

Exclusion Criteria

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

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I have brain metastases that have not been treated.

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I am on medication for an autoimmune disease.

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I had a severe reaction to previous immunotherapy.

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I currently have an infection that isn't under control.

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I have had a kidney or another solid organ transplant.

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I am taking more than 10 mg of prednisone or its equivalent daily.

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I am not using any experimental treatments or therapies for MCC.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 1 year post infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 1 year post infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 1 year post infusion for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Best overall response

Incidence of adverse events grade 3 or higher determined to be possibly, probably or definitely secondary to any of the study treatments

Secondary study objectives

Overall survival

Progression-free survival

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Treatment 2 (TCR-T cells, avelumab or pembrolizumab)Experimental Treatment4 Interventions

Approximated 5-7 days prior to receiving FH-MCVA2TCR T-cells, patients receive interferon gamma administered at the FDA-approved dosing of 50mcg/m2, 3 times weekly for a total of 4 weeks. Patients receive FH-MCVA2TCR T-cells IV over 60-120 minutes. Beginning 14 days after receiving FH-MCVA2TCR T-cells, patients also receive standard of care avelumab IV over 1 hour every 2 weeks for 1 year or pembrolizumab IV over 30 minutes every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease may then receive an additional cycle of FH-MCVA2TCR T-cells.

Group II: Treatment (TCR-T cells, avelumab or pembrolizumab)Experimental Treatment4 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Avelumab

2017

Completed Phase 2

~2440

Pembrolizumab

2017

Completed Phase 3

~3150

Interferon Gamma-1b

2013

Completed Phase 2

~50

0 / 18Eligibility 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 skin conditions often involve immune modulation to enhance the body's ability to fight disease. For example, topical immunotherapy agents like DPCP and SADBE are used to treat alopecia areata by inducing a mild allergic reaction that stimulates hair regrowth. Similarly, gene-modified immune cells, such as FH-MCVA2TCR, are designed to enhance the immune response against cancer cells in Merkel cell cancer. These treatments matter for patients with other skin conditions because they represent a shift towards harnessing the body's immune system to target and treat diseases, potentially offering more effective and personalized therapeutic options.

What kind of rash is it?: deciphering the dermatologic toxicities of biologic and targeted therapies.