Cell Therapy for Sarcoma

Recruiting at 43 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Adaptimmune

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: CNS metastases, Prior malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

7 Participants Needed

Trial Summary

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

The trial protocol does not specify if you need to stop taking your current medications. However, there are washout periods for prior radiotherapy and systemic chemotherapy, which means you may need to stop these treatments for a certain time before starting the trial.

What data supports the effectiveness of the treatment Lete-Cel for sarcoma?

Lete-Cel, a type of cell therapy, has shown promise in treating metastatic synovial sarcoma with a 50% overall response rate in a study involving 45 patients. This suggests that Lete-Cel could be an effective treatment option for this type of sarcoma. ^{1 2 3 4 5}

Is cell therapy for sarcoma, like Lete-Cel, generally safe for humans?

Cell therapies like CAR-T cell treatments have been used safely in humans for other conditions, such as certain types of lymphoma. Common side effects include cytokine release syndrome (a strong immune reaction) and neurological issues, but these are usually manageable with proper medical care. ^{6 7 8 9 10}

How is the treatment Lete-Cel unique for sarcoma?

Lete-Cel is a type of cell therapy that uses genetically modified T-cells to target specific proteins on sarcoma cells, which is different from traditional treatments that rely on chemotherapy or radiation. This approach is similar to CAR-T cell therapy, which has shown success in other cancers, and offers a novel way to treat sarcomas, especially those that are recurrent or metastatic. ^{2 10 11 12 13}

What is the purpose of this trial?

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors. This trial is a sub study of the Master study NCT03967223.

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for people over 10 years old with advanced synovial sarcoma or myxoid/round cell liposarcoma, which are types of tumors. Participants must have certain HLA-A2 genes and their tumor must express NY-ESO-1. They should be relatively healthy (good performance status) and not have had severe autoimmune diseases, previous specific cancer treatments, major surgery within the last month, or other serious health issues.

Inclusion Criteria

My genetic test shows I have HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06.

My tumor is positive for NY-ESO-1.

I am mostly active and can carry out daily activities with little to no help.

Exclusion Criteria

Prior radiation exceeds protocol specified limits

My cancer has spread to my brain.

I have a cancer that is not fully in remission.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive human engineered T-cell therapies for advanced tumors

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 54 months

Treatment Details

Interventions

• Lete-Cel

Trial Overview The study tests Letetresgene autoleucel (lete-cel), a type of engineered T-cell therapy designed to target cancer cells in patients with specific genetic markers. It's part of a larger study on human-engineered T-cell therapies. Patients will also receive Cyclophosphamide and Fludarabine as part of the treatment process.

Participant Groups

Group I: Letetresgene autoleucel Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Adaptimmune

Lead Sponsor

Trials

25

Recruited

10,000+

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

CAR T Cell therapy is a promising new treatment for sarcomas, which have seen stagnant survival rates, particularly in recurrent or metastatic cases, highlighting the urgent need for novel therapies.

Recent studies have identified several sarcoma-associated antigens suitable for CAR T Cell targeting, such as HER2 and GD2, showing encouraging results and suggesting that this therapy could improve outcomes for sarcoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. Thanindratarn, P., Dean, DC., Nelson, SD., et al.[2020]

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]

In a study involving 14 Japanese patients with relapsed or refractory aggressive large B-cell lymphoma, the CAR T-cell therapy lisocabtagene maraleucel (liso-cel) showed a 70% objective response rate and a 50% complete response rate, indicating significant efficacy.

The treatment had a manageable safety profile, with common side effects including neutropenia (90%) and cytokine release syndrome (50%), but no severe (grade ≥3) cytokine release syndrome events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. Makita, S., Yamamoto, G., Maruyama, D., et al.[2023]

Tisagenlecleucel, an anti-CD19 CAR-T cell therapy, has been approved for treating pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), showing significant long-term effectiveness and overall survival benefits.

While CAR-T cell therapy can lead to serious adverse events like cytokine release syndrome and neurological toxicities, these effects are manageable with proper medical training and protocols, highlighting the importance of specialized care in administering this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. Buechner, J., Kersten, MJ., Fuchs, M., et al.[2020]

In a study of 91 patients with relapsed/refractory large B-cell lymphoma (LBCL), treatment with the CAR T-cell therapy tisagenlecleucel (tisa-cel) resulted in a best overall response rate of 60% and a complete response rate of 32%, indicating its efficacy in a real-world setting.

The safety profile of tisa-cel was manageable, with only 5% of patients experiencing severe cytokine release syndrome and 1% experiencing neurotoxicity, suggesting that it can be safely administered in standard-of-care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Iacoboni, G., Villacampa, G., Martinez-Cibrian, N., et al.[2021]

The manufacturing process for lisocabtagene maraleucel (liso-cel), an autologous CAR T-cell therapy, has been optimized to ensure high product quality and consistency, even with diverse starting materials from patients with various hematologic malignancies.

Improvements in the manufacturing process led to over 95% T-cell purity and enhanced viability of the CAR T-cell product, demonstrating that liso-cel can effectively maintain its therapeutic potential despite variability in patient-derived materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. Teoh, J., Brown, LF.[2022]

The phase 1 trial showed that NY-ESO-1-specific TCR-T cells are both safe and effective for treating advanced soft tissue sarcomas, marking a significant advancement in adoptive T cell therapy.

This study represents an important step in the clinical application of T cell therapies, potentially offering new hope for patients with this challenging type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pushing forward in sarcoma with a new TCR targeting NY-ESO-1. Al-Marayaty, R., Pollack, SM.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Biomarker correlates with response to NY-ESO-1 TCR T cells in patients with synovial sarcoma. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T (CAR-T) cell immunotherapy for sarcomas: From mechanisms to potential clinical applications. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Innovative Breakthroughs for the Treatment of Advanced and Metastatic Synovial Sarcoma. [2023]

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

Patient-derived xenografts for individualized care in advanced sarcoma. [2022]

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

Phase 2 results of lisocabtagene maraleucel in Japanese patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. [2023]

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

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020]

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

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Developing lisocabtagene maraleucel chimeric antigen receptor T-cell manufacturing for improved process, product quality and consistency across CD19+ hematologic indications. [2022]

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

Pushing forward in sarcoma with a new TCR targeting NY-ESO-1. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Ewing sarcoma dissemination and response to T-cell therapy in mice assessed by whole-body magnetic resonance imaging. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy for sarcoma. [2018]

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

Donor lymphocyte infusions in adolescents and young adults for control of advanced pediatric sarcoma. [2022]