Cell Therapy for Sarcoma

Not currently recruiting at 49 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called Lete-Cel to determine its safety and effectiveness in treating certain advanced cancers. It targets individuals with specific types of sarcoma, which originate in the bones or soft tissues. Participants must have a specific genetic makeup (certain proteins in their body) and a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma. The trial aims to discover if this treatment can shrink tumors or slow their growth. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Lete-Cel is likely to be safe for humans?

Studies have shown that Lete-Cel, the treatment being tested, generally causes manageable side effects. In some research, almost all patients experienced treatment-related side effects, but these were usually not severe. Common side effects included low blood cell counts and immune system reactions. Importantly, no deaths related to the treatment have been reported.

Previous trials with Lete-Cel in other cancers, such as multiple myeloma and lung cancer, found similar results. Most side effects were manageable and did not lead to serious problems. This suggests that while side effects are common, they are usually mild and controllable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for sarcoma, which often include surgery, chemotherapy, and radiation, Lete-Cel is unique because it uses a personalized cell therapy approach. This treatment involves engineering a patient's own immune cells to better recognize and attack cancer cells. Researchers are excited about Lete-Cel because it represents a targeted therapy that could offer more precise and potentially effective treatment by harnessing the body's own immune system against the cancer.

What evidence suggests that Lete-Cel might be an effective treatment for sarcoma?

Research has shown that letetresgene autoleucel, or lete-cel, may help treat certain types of sarcoma, a kind of cancer. In previous studies, lete-cel had a 42% response rate for synovial sarcoma and myxoid/round cell liposarcoma, meaning nearly half of the patients experienced their tumors shrinking or not growing. Another study found a 50% overall response rate, including patients who had significant health improvements. Patients treated with lete-cel also had a median progression-free survival of several months, indicating that the treatment helped slow the cancer's growth. These results suggest that lete-cel could be a promising option for people with advanced sarcoma. Participants in this trial will receive lete-cel to further evaluate its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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 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]

Citations

1. onclive.com onclive.com/view/lete-cel-generates-durable-responses-in-synovial-sarcoma-and-myoxid-round-cell-liposarcoma

Lete-Cel Generates Durable Responses in Synovial ... The median progression-free survival (PFS) was 5.3 months (95% CI, 4.0-8.0), 3.9 months (95% CI, 2.6-7.8), and 7.7 months (95% CI, 5.2-9.2) in ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01466

Letetresgene Autoleucel in Advanced/Metastatic Myxoid ... Median OS follow-up for cohort 2 was 30.4 months (95% CI, 12.9 to 36.8), with probability of survival at 12, 24, and 30 months being 90% (95% CI ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10111356/

Safety and efficacy of letetresgene autoleucel alone or with ... Pooled overall response rate was 50% including 1 patient each with confirmed clinical response, very good clinical response, and partial response, and ...

4. curetoday.com curetoday.com/view/t-cell-therapy-with-lete-cel-demonstrates-efficacy-in-sarcoma-subtypes

T-Cell Therapy With Lete-Cel Demonstrates Efficacy in ... Letetresgene autoleucel (lete-cel) showed a 42% response rate in a phase 2 trial for synovial sarcoma and myxoid/round cell liposarcoma. The ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT381489

Primary efficacy and safety of letetresgene autoleucel (lete- ... The median follow-up was 5.6 (C1) and 12.9 (C2) mo. In C1 the IA ORR was 20%, with best response (BR) of partial response (PR) in 2 pts and BR of stable disease ...

6. aacrjournals.org aacrjournals.org/clincancerres/article/31/3/529/751208/Safety-and-Tolerability-of-Letetresgene-Autoleucel

Pilot Studies in Patients with Advanced Non–Small Cell Lung ... Lete-cel demonstrated a manageable safety profile. No fatal treatment-related serious adverse events (AE) were reported in either study. Cytopenias and cytokine ...