NK Cell Therapy + Chemotherapy for Sarcoma

Overseen By John Livingston, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Immunosuppressants, Anticancer agents

Disqualifiers: Infections, Hepatitis, HIV, Autoimmune, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-6 weeks

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment that combines NK cells (a type of immune cell) with chemotherapy to determine the safest dose for people with advanced cancers, such as certain types of sarcoma. The goal is to evaluate the effectiveness and safety of this combination. It suits patients with advanced solid tumors who have not responded to standard treatments and have specific markers in their cancer that the study targets. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial requires that you stop taking certain medications before starting. You must be at least 2 weeks from your last chemotherapy and stop any tyrosine kinase inhibitors or targeted therapies at least 3 days before starting the trial's chemotherapy. If you're on systemic steroids, you may need to adjust your dose.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the NY-ESO-1 TCR/IL-15 NK cell therapy is undergoing safety testing for advanced cancers like synovial sarcoma and myxoid liposarcoma. Early studies focus on determining the optimal dose and evaluating the effectiveness of these specially engineered cells.

Although data from past trials remains limited, the FDA has approved the treatment for human testing, indicating it has passed basic safety checks for trial use. As an early-phase trial, the primary goal is to identify a safe dose, with close monitoring of side effects. If serious side effects occur at a certain dose, researchers will test a lower dose to find one that is safe and well-tolerated.

In summary, while the treatment's safety is still under evaluation, reaching this stage suggests potential safety in earlier studies. Participants in this trial will contribute to understanding its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for sarcoma?

Unlike the standard treatments for sarcoma, which typically involve surgery, radiation, and chemotherapy, the NK Cell Therapy + Chemotherapy approach is innovative because it combines a specific type of immunotherapy with chemotherapy. Researchers are excited about this treatment because it uses NY-ESO-1 TCR/IL-15 NK cells, which are engineered to enhance the body's immune response against cancer cells by targeting a specific antigen found in sarcoma. This approach is unique as it not only aims to directly attack cancer cells but also boosts the patient’s immune system to recognize and fight the tumor more effectively. This dual-action method could potentially improve outcomes for patients for whom traditional treatments are less effective.

What evidence suggests that this trial's treatments could be effective for sarcoma?

Research shows that a new treatment using NY-ESO-1 TCR/IL-15 NK cells could help treat sarcoma, a type of cancer. These cells are specially designed to find and attack a protein called NY-ESO-1, often present in certain sarcomas. Earlier studies found this protein in 88% of myxoid liposarcomas and 49% of synovial sarcomas, making it a good target for treatment. The goal is to strengthen the body's immune response to fight the cancer cells. Early results suggest that these engineered NK cells might improve outcomes by directly attacking the cancer. More research is needed to confirm these effects and determine the best dose. ^{2 3 4 5 6}

Who Is on the Research Team?

John A Livingston, MD MS

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for people aged 16-80 with advanced sarcomas, specifically synovial or myxoid/round cell liposarcoma, who've tried at least one standard treatment without success. They must have proper liver, kidney, heart, and blood function and no serious infections or autoimmune diseases. Participants need to be HLA-A*02 positive with NY-ESO-1 expression in tumors.

Inclusion Criteria

My organs are functioning well according to my recent tests.

My cancer expresses NY-ESO-1 and I have specific HLA types.

My cancer is either synovial sarcoma or myxoid/round cell liposarcoma, tests positive for specific HLA types, and shows high NY-ESO-1 expression.

Exclusion Criteria

- Uncontrolled arrhythmia, considered per PI

I have an active neurological disorder.

I have serious side effects from past cancer treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to NK cell infusion

1-2 weeks

Treatment

Participants receive adoptive NK cells expressing an affinity-enhanced T-cell receptor (TCR) reactive against the NY-ESO-1

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine phosphate
• NY-ESO-1 TCR/IL-15 NK

Trial Overview

The study tests the safety and optimal dose of donated NK cells expressing a TCR against NY-ESO-1 combined with chemotherapy (Cyclophosphamide and Fludarabine phosphate) in patients with specific advanced cancers to see how well they tolerate it and its effects on their disease.

How Is the Trial Designed?

Group I: Dose escalation - Inpatient and Outpatient Experimental Treatment 3 Interventions

Participants will be assigned to receive a dose level of NK cells based on when the participants joins the study. Up to 6 participants will be enrolled at each dose level. If no intolerable side effects are seen after the first 3-6, the next group of participants will get at higher dose. Up to 4 dose levels of NK cells will be tested. If the first dosing group shows intolerable side effects, a lower dose will be tested.

NY-ESO-1 TCR/IL-15 NK is already approved in United States for the following indications:

Approved in United States as NY-ESO-1 TCR/IL-15 NK for:

• Multiple Myeloma
• Synovial Sarcoma
• Myxoid/Round Cell Liposarcoma

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

In a phase I clinical trial involving four patients with synovial sarcoma and myxoid/round cell liposarcoma, NY-ESO-1-specific endogenous T cell therapy was well tolerated without significant toxicity, although all patients experienced disease progression.

Despite the presence of NY-ESO-1-specific T cells in the blood, these cells showed limited activation and proliferation; however, they could be stimulated to become active using IL-15, suggesting a potential strategy to enhance the effectiveness of adoptive cellular therapy in future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-15 mediated expansion of rare durable memory T cells following adoptive cellular therapy. Kohli, K., Yao, L., Nowicki, TS., et al.[2022]

In a study involving 8 patients with advanced or recurrent synovial sarcoma, the infusion of autologous T lymphocytes expressing NY-ESO-1 T-cell receptors showed a promising objective response rate of 50%, indicating potential efficacy in targeting this type of cancer.

While all patients experienced adverse events, the treatment was considered safe, with no deaths linked to these events and manageable cases of cytokine release syndrome, suggesting that TBI-1301 could be a viable option for patients resistant to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of NY-ESO-1 Antigen-specific T-cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial. Kawai, A., Ishihara, M., Nakamura, T., et al.[2023]

Transgenic adoptive cell therapy (ACT) using NY-ESO-1-specific T cells combined with dendritic cell vaccination showed promising results, with 66% of patients in the ESO cohort and 50% in the INY cohort experiencing tumor regression.

The study indicated that while the combination of ACT and dendritic cell vaccination is feasible and leads to some antitumor activity, adding the immune checkpoint inhibitor ipilimumab did not provide additional clinical benefits, suggesting that further improvements are needed to sustain tumor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Trial of the Combination of Transgenic NY-ESO-1-reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab. Nowicki, TS., Berent-Maoz, B., Cheung-Lau, G., et al.[2023]

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]

A 68-year-old man with synovial sarcoma showed a 34.9% reduction in tumor size after TCR-T therapy targeting the NY-ESO-1 protein, but disease progression occurred shortly after treatment, highlighting the challenge of resistance to TCR-T therapy.

The study found that beta-catenin levels were up-regulated in recurrent tumor tissues after TCR-T therapy, suggesting it may play a role in T-cell exclusion and resistance, indicating a potential area for further research in improving TCR-T efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histological Assessment of Synovial Sarcoma Before and After TCR-T Cell Therapy and Cryoablation: A Case Report. Asanuma, K., Ishihara, M., Nakamura, T., et al.[2023]

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]

Combining NY-ESO-1-specific T cells with histone deacetylase inhibitors (HDACis) like panobinostat or vorionstat enhances the effectiveness of these T cells against soft tissue sarcoma (STS) cells, as shown in ex vivo studies.

Pretreatment with HDACis increases the expression of the NY-ESO-1 antigen and HLA-ABC on STS cells, leading to improved T cell activation and cytokine release, suggesting a promising strategy to boost the efficacy of adoptive cell therapy in treating STS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma. Gong, W., Wang, L., Schubert, ML., et al.[2022]

The phase 1 clinical trial of TAEST16001, a TCR affinity-enhanced T cell therapy targeting NY-ESO-1, showed no serious treatment-related adverse events in 12 patients, indicating a safe therapeutic approach.

The therapy demonstrated an overall response rate of 41.7%, with a median progression-free survival of 7.2 months and a median duration of response of 13.1 months, highlighting its efficacy in treating advanced soft tissue sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma. Pan, Q., Weng, D., Liu, J., et al.[2023]

Ewing sarcoma (EWS) cells are susceptible to natural killer (NK) cell-mediated lysis, especially when NK cells are activated with interleukin-15 (IL-15), indicating a potential for immunotherapy in treating this cancer.

The effectiveness of NK cell cytotoxicity against EWS is primarily driven by the activation signals from receptors NKG2D and DNAM-1, suggesting that enhancing these pathways could improve therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways. Verhoeven, DH., de Hooge, AS., Mooiman, EC., et al.[2021]

Citations

1.

targetedonc.com

targetedonc.com/view/fda-clears-ind-of-prame-tcr-il-15-nk-program-for-r-r-myeloid-malignancies

FDA Clears IND of PRAME TCR-IL-15 NK Program for R ...

PRAME TCR/IL-15 NK is being developed by Syena. This is the second TCR-NK target from Syena following the NY-ESO-1-targeted TCR-NK program.

2.

cgtlive.com

cgtlive.com/view/md-anderson-syena-sarcoma-tcr-nk-cell-therapy-ind-clearance

MD Anderson and Syena's Sarcoma TCR NK Cell Therapy ...

A phase 1/1b clinical trial is planned to evaluate the safety and efficacy of the therapy.

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-08752

Genetically Engineered Cells (NY-ESO-1 TCR/IL-15 NK ...

This phase I/Ib trial tests the safety, best dose, and effectiveness of NY-ESO-1 T-cell receptor (TCR)/IL-15 cord blood-derived natural killer (NK) cells ...

4.

mdanderson.org

mdanderson.org/newsroom/novel-tcr-nk-cell-therapy-sarcoma-receives-ind-clearance-fda.h00-159619434.html

Novel TCR NK cell therapy for sarcoma receives IND ...

The Phase I/Ib study will assess the safety and efficacy of NY-ESO-1 TCR/IL-15 NK in patients with synovial sarcoma and myxoid/round cell ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10439245/

Phase 1 clinical trial to assess safety and efficacy of NY-ESO ...

NY-ESO-1 has been considered a potential target of immunotherapy in sarcomas and is reported to be expressed in 88% of myxoid liposarcomas, 49% ...

6.

cgtlive.com

cgtlive.com/view/md-anderson-syena-tcr-nk-cell-therapy-another-ind-clearance-multiple-myeloma

MD Anderson and Syena's TCR NK Cell Therapy Gets ...

NY-ESO-1 TCR/IL-15 NK previously received clearance of an IND for advanced synovial sarcoma and myxoid/round cell liposarcoma in June 2023.