Adoptive T Cell Therapy for Melanoma

Overseen By Ann Lau Clark, RN, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Loyola University

Must not be taking: Steroids, Antibiotics

Disqualifiers: Pregnancy, Brain metastases, Severe disease, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for advanced melanoma, a type of skin cancer that has spread to other parts of the body. Researchers are testing Autologous TIL 1383I TCR Gene Modified T Cells, which are immune cells altered to better fight cancer. The study aims to determine the safest dose of these T cells for future trials. Candidates for this trial have metastatic melanoma that continues to grow or spread despite other treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients taking steroids for disease control or pain management are excluded. It also requires a waiting period after certain treatments, like a 6-week gap after anti-CTLA-4 treatment and a 4-week gap after anti-PD-1 or anti-PD-L1 treatment.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that TIL 1383I TCR gene-modified T cells may help treat advanced melanoma. These cells are specifically designed to target melanoma cells. Early results suggest that these cells remain active in the body for some time after administration.

Some studies found that this treatment did not cause serious side effects in patients, indicating it might be well-tolerated. However, it's important to note that this is an early-stage trial. Phase 1 trials primarily focus on determining the safest dose, so information on safety might still be limited.

For those considering joining this trial, it is reassuring that researchers strive to balance effectiveness and safety. Always consult your doctor to understand what this could mean for you. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for melanoma, which often include surgery, chemotherapy, and targeted therapies, the investigational treatment uses autologous TIL 1383I TCR gene-modified T cells. These are T cells engineered to better recognize and attack melanoma cells, providing a more personalized and potentially more powerful immune response. Researchers are excited about this approach because it represents a novel way to harness the body's own immune system to fight cancer more effectively. By modifying the T cells to boost their cancer-fighting capabilities, this treatment could potentially offer a new hope for patients with advanced melanoma who haven't responded well to conventional therapies.

What evidence suggests that this treatment might be an effective treatment for melanoma?

Research has shown that a new treatment using specially modified T cells could help treat advanced melanoma, a type of skin cancer. These T cells are designed to find and attack melanoma cells. In earlier studies, researchers found these modified T cells in patients after treatment, suggesting they can remain active and continue fighting the cancer. This treatment uses a combination of T cells trained to locate and destroy tumor cells. Early evidence suggests this method can enhance the body's ability to fight melanoma. ^{1 2 3 4 5}

Who Is on the Research Team?

Michael Nishimura, PhD

Principal Investigator

Loyola University

Are You a Good Fit for This Trial?

Adults with advanced melanoma that can be measured, who are in good physical condition (ECOG PS of 0 or 1), and have tried certain treatments without success. They must not be pregnant, vulnerable individuals, or have severe infections or other health conditions that could interfere with the trial.

Inclusion Criteria

Patients must consent to be in the study and must have signed and dated an approved consent form, which conforms to federal and institutional guidelines.

My melanoma has spread and can be measured by tests or seen on scans.

My heart and lungs are strong enough for IL-2 treatment.

Exclusion Criteria

I have not had active brain melanoma or treatment for it in the last 3 months.

Your blood test results show low levels of white blood cells or platelets, or high levels of certain liver or kidney markers.

Special classes of subjects such as fetuses, pregnant women, children, prisoners, institutionalized individuals, or others who are likely to be vulnerable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive escalating doses of TIL 1383I TCR transduced T cells to determine the maximum tolerated dose

4 weeks

3 visits (in-person) for each cohort

Follow-up

Participants are monitored clinically and immunologically for safety and effectiveness after T cell infusion

1 year

Regular visits (in-person) over the year

What Are the Treatments Tested in This Trial?

Interventions

• Autologous TIL 1383I TCR Gene Modified T Cells

Trial Overview This Phase I trial is testing escalating doses of genetically modified T cells to treat advanced melanoma. It's funded by the NCI and aims to find the right dose for Phase II trials. Participants receive a retrovirus-modified version of their own T cells.

How Is the Trial Designed?

Group I: Escalating Doses Experimental Treatment 1 Intervention

Three patients will be treated at the first \& each subsequent dose level. Patients will be observed for 30 days post T cell infusion. If there was one DLT in the first 3 patients, an additional 3 patients will be treated at that level. If no additional DLTs are observed (for a total of 1 DLT in 6 patients) then the dose will be escalated. If two patients in the first 3 patients at a dose level experience a DLT, the dose will be de-escalated to the previous level \& an additional 3 patients will be enrolled at that level if 6 have not yet been treated at that level. The maximum tolerated dose (MTD) is defined as the highest dose at which 0 or 1 patient in six has experienced a DLT. If 2 or 3 patients in the first 3 patients experience a DLT at the first dose level, the study will terminate.

Who Is Running the Clinical Trial?

Loyola University

Lead Sponsor

Trials

161

Recruited

31,400+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase I/IIa trial involving 12 patients with metastatic melanoma, the adoptive transfer of T cells expressing a MART-1-specific TCR showed partial responses in 18% of assessable patients, indicating some efficacy in targeting the cancer.

However, the study was prematurely terminated due to significant dose-dependent toxicities, including severe skin, eye, and ear reactions, as well as cytokine release syndrome, highlighting safety concerns with higher doses of TCR-modified T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MART-1 TCR gene-modified peripheral blood T cells for the treatment of metastatic melanoma: a phase I/IIa clinical trial. Rohaan, MW., Gomez-Eerland, R., van den Berg, JH., et al.[2022]

Adoptive T-cell therapy (ACT) has shown the ability to induce complete and lasting tumor regression in certain cancers, particularly metastatic melanoma, with some patients potentially being cured.

Recent advancements in identifying mutated gene products as targets for TILs and the use of engineered T cells (like those expressing chimeric antigen receptors) suggest that ACT could be expanded to treat a wider range of malignancies beyond melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting the curative potential of adoptive T-cell therapy for cancer. Hinrichs, CS., Rosenberg, SA.[2023]

TCR gene-modified T lymphocytes can be produced to target specific antigens, showing promise in treating persistent viral infections and cancer, with successful protection observed in animal models.

A human trial demonstrated that TCR gene-modified T cells persisted in all participants and reduced melanoma burden in 2 out of 15 patients, indicating potential for clinical application despite the need for further optimization in T-cell differentiation and expansion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal T-cell receptors: new reagents for cancer therapy. Stauss, HJ., Cesco-Gaspere, M., Thomas, S., et al.[2022]

A specific T-cell receptor (TCR) targeting the melanoma antigen tyrosinase was successfully introduced into normal human T cells, enabling them to recognize and attack melanoma cells.

The engineered T cells not only secreted cytokines in response to melanoma cells but also demonstrated the ability to kill these cancer cells, highlighting the potential of this TCR for effective adoptive immunotherapy against melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous generation of CD8+ and CD4+ melanoma-reactive T cells by retroviral-mediated transfer of a single T-cell receptor. Roszkowski, JJ., Lyons, GE., Kast, WM., et al.[2007]

Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown significant promise in treating melanoma, leading to durable responses and extended survival for patients.

Recent advancements in genetic modifications, such as T-cell receptor (TCR) engineering and chimeric antigen receptors (CARs), may enhance the effectiveness of immunotherapy in melanoma, although CAR T-cell therapies have had limited success in solid tumors so far.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive Cell Therapy for Metastatic Melanoma. Merhavi-Shoham, E., Itzhaki, O., Markel, G., et al.[2018]

Adoptive T-cell therapy using tumor-infiltrating lymphocytes (TILs) has shown significant promise in treating metastatic melanoma, leading to the development of genetically engineered T cells that can specifically target tumor-associated antigens (TAAs).

Initial clinical studies indicate that these genetically engineered T cells, including those with tumor antigen-specific T cell receptors (TCRs) and chimeric antigen receptors (CARs), can effectively cause tumor regression, although safety concerns, particularly regarding potential 'on-target, off-organ' toxicity, must be carefully managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the efficacy and safety of engineered T cell therapy for cancer. Shi, H., Liu, L., Wang, Z.[2020]

T-cell receptor (TCR) gene-modified T cells can effectively cure mice with disseminated leukemia in a murine model of adoptive T-cell immunotherapy, showcasing the potential of this approach for treating human cancers.

To enhance the long-term effectiveness of TCR-modified T cells, activating these cells through their endogenous TCR can boost the expression of the introduced TCR, potentially leading to a stronger and more persistent antitumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy of disseminated leukemia with TCR-transduced, CD8+ T cells expressing a known endogenous TCR. Dossett, ML., Teague, RM., Schmitt, TM., et al.[2021]

Adoptive cell transfer using tumor-infiltrating lymphocytes (TIL) has shown a significant response rate of about 50% in patients with metastatic melanoma, indicating its potential as an effective treatment.

Genetically modifying T lymphocytes with T-cell receptors (TCR) targeting tumor antigens has demonstrated objective responses in melanoma, suggesting this approach could be expanded to treat other common epithelial cancers beyond melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Application of gene therapy in tumor adoptive immunotherapy]. Wang, C., Zhao, Y.[2012]

A phase 1 trial showed that transferring specific T-cell receptor (TCR) genes into a patient's own lymphocytes can generate tumor-reactive T cells, but the response rate was lower than expected compared to tumor-infiltrating lymphocyte infusions.

The study developed methods to enhance TCR expression and selected a high-affinity TCR for melanoma, demonstrating improved in vivo function and safety, which could lead to more effective TCR gene therapies in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selecting highly affine and well-expressed TCRs for gene therapy of melanoma. Jorritsma, A., Gomez-Eerland, R., Dokter, M., et al.[2021]

Adoptive T cell therapy using tumor-infiltrating lymphocytes (TIL) shows promise for cancer treatment, particularly in targeting melanoma, and can be enhanced through genetic modification to improve their effectiveness.

An optimized protocol for retroviral transduction of TIL resulted in 69% of TIL expressing a chimeric antigen receptor (CAR), which significantly improved their ability to respond to CD19+ cancer cells, demonstrating the potential for increased therapeutic efficacy in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic Modification of Tumor-Infiltrating Lymphocytes via Retroviral Transduction. Weinstein-Marom, H., Gross, G., Levi, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3991194/

TIL 1383I TCR transduced T-cells are detectable after infusion Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion · Background · Methods · Results.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02870244

Adoptive T Cell Immunotherapy for Advanced Melanoma ... Autologous bulk TIL 13831 TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4 + and CD8+ T Cells expressing the TIL 13831 TCR.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01586403

Transfer of Genetically Engineered Lymphocytes in ... Autologous bulk TIL 1383I TCR transduced T cells means the infusion will consist of a polyclonal mixture of CD4+ and CD8+ T cells expressing the TIL 1383I TCR.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8949949/

Genetic Modification of T Cells for the Immunotherapy of Cancer Adoptive transfer of T cells is an effective method to provide patients with a source of T cells (autologous or allogenic) capable of targeting their tumor ...

5. cancer.gov cancer.gov/publications/dictionaries/cancer-drug/def/til-1383i-t-cell-receptor-transduced-autologous-t-cells

TIL 1383I T cell receptor-transduced autologous T cells TIL 1383I TCR originated from a melanoma patient's CD4+ tumor-infiltrating lymphocytes and is reactive against a class I MHC (HLA-A2)-restricted epitope (368- ...