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

Trial Summary

What is the purpose of this trial?

To find a recommended dose of attIL2-TIL cell therapy that can be given to participant with either relapsed or metastatic sarcomas (has come back or spread to other parts of the body, respectively). To further test the dose found in Part A to see if it can help to control liposarcoma growth.

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.

What data supports the effectiveness of this treatment for sarcoma?

Research shows that tumor-infiltrating lymphocytes (TILs) can be successfully isolated and expanded from sarcoma tumors, suggesting potential for TIL therapy in sarcoma. Additionally, TIL therapy has shown promising results in treating metastatic melanoma, with clinical response rates of 50% or more, indicating potential effectiveness in other cancers like sarcoma. ^{1 2 3 4 5}

What safety data exists for Modified TIL Cell Therapy in humans?

Studies on TIL cell therapy, including those for melanoma and osteosarcoma, show that it is generally well-tolerated in humans. Common side effects include fever and temporary drops in blood cell counts, but no serious long-term adverse effects have been reported. ^{1 6 7 8 9}

What makes the modified TIL cell therapy unique for treating sarcoma?

This treatment is unique because it uses modified tumor-infiltrating lymphocytes (TILs) that are engineered to target tumors more effectively by anchoring a tumor-targeted IL12, which enhances their anti-tumor activity. Unlike conventional therapies, this approach is personalized and leverages the body's immune system to fight cancer, offering a potential new option for sarcoma patients who have limited benefits from standard treatments. ^{1 7 10 11 12}

Research Team

Neeta Somaiah, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Investigating the Potential of Isolating and Expanding Tumour-Infiltrating Lymphocytes from Adult Sarcoma. [2022]

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

White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy. [2020]

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

Immunotherapy of sarcomas with modified T cells. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Analysis of tumor-infiltrating NK and T cells highlights IL-15 stimulation and TIGIT blockade as a combination immunotherapy strategy for soft tissue sarcomas. [2021]

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

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. [2022]

6. Egypt pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Engineered artificial antigen presenting cells facilitate direct and efficient expansion of tumor infiltrating lymphocytes. [2021]

8. China pubmed.ncbi.nlm.nih.gov

[An exploratory clinical study of the efficacy and safety of tumor-infiltrating lymphocytes in the treatment of metastatic osteosarcoma]. [2022]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Exploiting the curative potential of adoptive T-cell therapy for cancer. [2023]

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

Activation and propagation of tumor-infiltrating lymphocytes on clinical-grade designer artificial antigen-presenting cells for adoptive immunotherapy of melanoma. [2021]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. [2020]