Modified TIL Cell Therapy for Sarcoma

Overseen By Neeta Somaiah, MBBS

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: Unknown

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a new cell therapy for treating sarcomas that have returned or spread. The therapy, known as T Cell Membrane-Anchored Tumor-Targeted IL12-Modified TIL Cell Therapy, uses specially modified immune cells to target and fight cancer. After establishing a safe dose in the initial phase, the trial will assess whether this dose can control the growth of liposarcoma, a type of sarcoma. Suitable candidates for this trial include individuals with advanced or metastatic sarcomas who have undergone at least one previous treatment and are scheduled for surgery or biopsy as part of their standard care. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not be on any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment at the time of tumor tissue collection or cell infusion. It's best to discuss your specific medications with the trial team.

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

Studies have shown that IL-12-based T-cell therapy for large solid tumors can be safe. This treatment, known as T Cell Membrane-Anchored Tumor-Targeted IL12-Modified TIL Cell Therapy, is new and closely monitored for side effects. Previous research suggests that, although still under study, it has been well-tolerated in other trials.

Researchers have carefully recorded and assessed any side effects in these studies to understand their impact. As this is an early phase clinical trial, the main goal is to learn about safety and determine the right dose. While the treatment is still under evaluation, early results are promising regarding patient tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sarcoma?

Unlike the standard treatments for sarcoma, which often involve chemotherapy, radiation, or surgery, the modified TIL (Tumor-Infiltrating Lymphocyte) cell therapy is exciting because it harnesses the body's own immune system to fight the cancer. This therapy uses T cells that are engineered to express a tumor-targeted IL12, a protein that can boost their cancer-fighting abilities. Researchers are particularly excited because this method directly targets the tumor cells, potentially leading to more effective and personalized treatment with fewer side effects than traditional options.

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

Research has shown that a new treatment called attIL12-TIL holds promise for sarcomas, a type of cancer that begins in bones or soft tissues. This therapy uses specially modified immune cells, known as T cells, to better target and attack cancer cells. In this trial, participants in Part A will receive varying doses of attIL12-TIL cell therapy to determine the highest tolerable dose. Participants in Part B will receive the recommended dose identified in Part A. Studies have found that this method can safely deliver a strong immune booster, IL-12, directly to tumors, enhancing the immune system's ability to fight cancer. Early results suggest that this approach helps T cells penetrate deep into tumors, where they usually struggle to work effectively. This targeted method could potentially improve outcomes for patients with sarcoma that has returned or spread. ^{1 2 4 5 6}

Who Is on the Research Team?

Neeta Somaiah, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 12 and older with advanced or metastatic soft tissue or bone sarcoma, who have had at least one prior systemic therapy unless no standard treatment exists. Participants must be willing to use birth control and have adequate organ function. Pregnant women, those with certain health conditions like uncontrolled illnesses, a history of primary immunodeficiency, active infections, or autoimmune diseases are excluded.

Inclusion Criteria

I am 12 years old or older.

It's been over 2 weeks since I had radiation therapy on any cancer area not being tested.

I am a man willing to use birth control during and for 3 months after the study if my partner can become pregnant.

Exclusion Criteria

My side effects from previous cancer treatments are mild or managed, except for hair loss or hearing loss.

I have had a primary immunodeficiency, organ transplant, or tuberculosis.

I have not received a live vaccine in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Determine the safety, maximum tolerated dose and/or recommended phase 2 dose of attIL12-TIL cell therapy in combination with cyclophosphamide

Variable, based on dose escalation

Treatment Part B

Characterize the safety and tolerability and assess preliminary efficacy of attIL12 TIL cells in combination with cyclophosphamide

4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• T Cell Membrane-Anchored Tumor-Targeted IL12 -Modified TIL Cell Therapy

Trial Overview

The study is testing the safety and effectiveness of attIL12-TIL cell therapy in patients with relapsed or metastatic sarcomas. It aims to determine an optimal dose that can manage liposarcoma growth. The trial includes pre-treatment with cyclophosphamide before administering the TIL cell therapy.

How Is the Trial Designed?

Group I: Part B Experimental Treatment 2 Interventions

Participants enrolled in Part B, will receive attIL2-TIL cell therapy at the recommended dose that was found in Part A.

Group II: Part A, Experimental Treatment 2 Interventions

Participants enrolled in Part A, the dose of attIL2-TIL cell therapy a participant receive will depend on when the participant joins this study. The first group of participants will receive the lowest dose level of attIL2-TIL cell therapy. Each new group will receive a higher dose of attIL2-TIL cell therapy than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of attIL2-TIL cell therapy is found.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

Tumor-infiltrating lymphocytes (TIL) have shown to be significantly more effective than other immune cells in treating advanced metastatic tumors, with successful expansion from 24 out of 25 human tumors, including various types of cancers.

The method developed for large-scale expansion of TIL resulted in generating over 10 billion lymphocytes in some cases, and clinical trials using these expanded TIL for treating metastatic disease have already commenced.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. Topalian, SL., Muul, LM., Solomon, D., et al.[2020]

Modified T-cell therapies, particularly those targeting cancer testis antigens like NY-ESO-1, show promising efficacy in treating sarcomas, with response rates of up to 60% observed in clinical trials for specific types like synovial sarcoma.

Challenges remain in the form of HLA-restriction and non-immunogenic tumor microenvironments, which may limit the effectiveness of these therapies, highlighting the need for further development to enhance T-cell specificity and persistence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy of sarcomas with modified T cells. Mahalingam, P., Julve, M., Huang, P., et al.[2023]

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]

In a phase II clinical trial involving 31 patients with metastatic melanoma, adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) resulted in a 48.4% objective clinical response rate, with 6.5% of patients achieving complete remission.

The study found that a higher number of infused TIL, particularly those with a greater proportion of CD8(+) T cells and a more differentiated effector phenotype, were significantly associated with better tumor regression outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Radvanyi, LG., Bernatchez, C., Zhang, M., et al.[2022]

Genetically-engineered artificial antigen presenting cells (aAPCs) can rapidly and effectively expand tumor-infiltrating lymphocytes (TILs) from cancer patients, achieving similar results to traditional methods but with a significantly lower feeder cell to TIL ratio.

The expanded TILs using aAPCs are tumor-reactive and maintain a favorable composition, with a higher proportion of CD8+ lymphocytes and lower frequencies of regulatory T cells, making them suitable for adoptive immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. Ye, Q., Loisiou, M., Levine, BL., et al.[2021]

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]

In a phase I/II trial involving 25 patients with treatment-refractory metastatic melanoma, adoptive cell transfer therapy using tumor-infiltrating lymphocytes (TIL) combined with a lower-dose IL2 regimen resulted in a 42% overall response rate, including three complete responses and seven partial responses.

The study demonstrated that while some classical IL2-related toxicities occurred, they were manageable outside of intensive care, suggesting that this attenuated IL2 approach may enhance safety while still achieving significant clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Andersen, R., Donia, M., Ellebaek, E., et al.[2021]

In a study involving 190 sarcoma tumor specimens, researchers successfully isolated tumor-infiltrating lymphocytes (TILs) from 54 of 92 primary sarcoma samples, indicating that certain sarcoma subtypes can provide enough TILs for potential immunotherapy.

The optimized protocol for expanding TILs demonstrated that these cells retained their ability to react and release IFNγ upon stimulation, suggesting their viability for future personalized immunotherapy treatments in sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma. Ko, A., Coward, VS., Gokgoz, N., et al.[2022]

Citations

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T Cell Membrane-Anchored Tumor-Targeted IL12 -Modified TIL Cell Therapy (attIL12-TIL) for Advanced/​Metastatic Soft Tissue and Bone Sarcoma Patients.

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Cell membrane-anchored and tumor-targeted IL-12 (attIL12)

This novel approach sheds light on the safe application of IL-12-based T-cell therapy for large and heterogeneous solid tumors.

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NCT05621668 | A First-In-Human Phase 1 Trial of T-Cell ...

Exploratory Objectives: Characterize the immune response following adoptive transfer of T cell membrane-anchored tumor targeted IL12 (attIL12)-T cells in paired ...

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Collagen-disrupting attIL12 TIL therapy boosts deep T cell ...

These results demonstrated that ctrl-TILs alone are not effective in penetrating PDX tumors (as in human patients), whereas the addition of attIL12 recovered ...

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T Cell Membrane-Anchored Tumor-Targeted IL12

Outcome Measure, Measure Description, Time Frame ; Safety and adverse events (AEs), Incidence of Adverse Events, Graded According to National Cancer Institute ...