Clinical Trials & Therapies

Trial ID: NCT06083883

Phase: 1/Ib

Status: Recruiting

Eligibility: Patients aged 16–80 with advanced synovial sarcoma expressing the NY-ESO-1 antigen and HLA-A*02 positive. Patients must have tumors that have progressed despite standard treatments.

Overview: This clinical trial evaluates a novel immunotherapy approach using natural killer (NK) cells genetically engineered to target NY-ESO-1, a protein commonly expressed by synovial sarcoma tumor cells. These modified NK cells are enhanced with interleukin-15 (IL-15) to improve their ability to persist and effectively destroy cancer cells. Patients receive chemotherapy conditioning before infusion of the engineered NK cells, which are designed to specifically recognize and attack tumors.

Preliminary Effectiveness: Although results from this specific study are pending, similar NK cell-based therapies have demonstrated promising early effectiveness in laboratory studies and initial clinical settings, showing potential for meaningful tumor responses.

More Information: https://clinicaltrials.gov/study/NCT06083883

Treatment Centers:
MD Anderson, TX, USA

Trial ID: NCT02601950

Phase: 2

Status: Recruiting

Eligibility: Adults with advanced or metastatic synovial sarcoma characterized by the SS18-SSX fusion gene. Participants must have measurable tumors and have experienced disease progression after prior therapies.

Overview: This Phase 2 trial investigates the effectiveness of tazemetostat, an oral medication that inhibits the EZH2 enzyme, which plays a critical role in the growth of synovial sarcoma. The study aims to determine whether tazemetostat can slow or halt tumor progression in patients with advanced synovial sarcoma.

Preliminary Effectiveness: Early results have shown promising disease stabilization, with mild side effects observed.

More Information: https://clinicaltrials.gov/ct2/show/NCT02601950

Treatment Centers:

• Dana-Farber, MA, USA
• Fred Hutch, WA, USA
• Mayo Clinic, MN, USA
• MSK, NY, USA
• Princess Margaret Cancer Centre, Toronto, Canada
• Gustave Roussy, Villejuif, France
• Royal Marsden Hospital, London, UK
• University Hospital Heidelberg, Heidelberg, Germany
• Peter MacCallum Cancer Centre, Melbourne, Australia

Trial ID: NCT06456359​

Phase: 2​

Status: Recruiting​

Eligibility: Individuals aged 13 to 50 with advanced synovial sarcoma or desmoplastic small round cell tumor expressing somatostatin receptors (SSTR2/3/5). Participants must have completed standard intensive treatment (chemotherapy, surgery, radiation) and have measurable disease.​

Overview: This Phase 2 trial evaluates pasireotide, a long-acting somatostatin analog, as maintenance therapy for synovial sarcoma and desmoplastic small round cell tumor. After standard intensive treatment, participants receive monthly pasireotide injections to assess its ability to prolong tumor control by targeting overexpressed somatostatin receptors (SSTR2/3/5) on tumor cells. ​

Preliminary Effectiveness: The trial aims to determine if pasireotide can delay or prevent relapse in these aggressive sarcomas.​

More Information: https://clinicaltrials.gov/study/NCT06456359​

Treatment Centers:

• University Hospital Heidelberg, Heidelberg, Germany

Trial ID: NCT04995003​

Phase: 1​

Status: Recruiting​

Eligibility: Patients with advanced or metastatic synovial sarcoma expressing the HER2 protein. Participants must have measurable tumors and have undergone prior standard therapies.​

Overview: This Phase 1 trial investigates the safety and preliminary effectiveness of combining HER2-targeted chimeric antigen receptor (CAR) T-cell therapy with immune checkpoint inhibitors (pembrolizumab or nivolumab) in patients with advanced synovial sarcoma. Participants' T cells are genetically engineered to target HER2-positive tumor cells. Following lymphodepleting chemotherapy, these modified T cells are infused back into the patient, accompanied by administration of a PD-1 inhibitor to enhance the immune response against cancer cells.​

Preliminary Effectiveness: Early-phase studies have demonstrated that HER2-targeted CAR T-cell therapy is safe and associated with clinical benefits in advanced sarcoma patients. 

More Information: https://clinicaltrials.gov/ct2/show/NCT04995003​

Treatment Centers:

• Texas Children's Hospital, Houston, TX, USA
• Baylor College of Medicine, Houston, TX, USA​
• University of California, Los Angeles (UCLA), Los Angeles, CA, USA

Trial ID: NCT05296564​

Phase: 1/2​

Status: Recruiting​

Eligibility: Adults aged 18 to 70 with metastatic or locally advanced synovial sarcoma expressing the NY-ESO-1 antigen. Participants must have measurable disease and have progressed after at least one prior line of therapy.​

Overview: This Phase 1/2 trial evaluates the safety and efficacy of HBI-0201-ESO TCR-T cells, an experimental therapy where patients' own T lymphocytes are genetically modified to express a T-cell receptor targeting the NY-ESO-1 antigen. Following lymphodepleting chemotherapy, these engineered T cells are infused back into the patient to target and attack NY-ESO-1–positive tumor cells. The study aims to assess the safety, proper dosing, and preliminary effectiveness of this personalized TCR therapy in patients with advanced synovial sarcoma and other NY-ESO-1–expressing metastatic cancers.​

Preliminary Effectiveness: As this is an ongoing first-in-human study, effectiveness data are pending. The trial seeks to determine safety, appropriate dosing, and early signs of efficacy.​

More Information: https://clinicaltrials.gov/ct2/show/NCT05296564​

Treatment Centers:

• Hadassah Medical Center, Jerusalem, Israel

Trial ID: NCT04535713​

Phase: 2​

Status: Recruiting​

Eligibility: Adults with unresectable or metastatic synovial sarcoma who are candidates for trabectedin therapy.​

Overview: This Phase 2 trial investigates biomarkers associated with response to trabectedin (Yondelis), a DNA-damaging chemotherapy approved for sarcoma treatment. Participants receive trabectedin as per standard care, with sequential tumor biopsies and blood tests conducted before and during therapy. The study aims to identify molecular markers that predict treatment efficacy, potentially guiding more personalized therapeutic approaches for synovial sarcoma patients.​

Preliminary Effectiveness: While trabectedin has demonstrated activity in various soft tissue sarcomas, including synovial sarcoma, this study focuses on biomarker identification to enhance treatment personalization.​

More Information: https://clinicaltrials.gov/ct2/show/NCT04535713​

Treatment Centers: 

• Sarcoma Oncology Research Center, Santa Monica, California, USA

Synovial Sarcoma Registry and Biospecimen Repository

Trial ID: NCT05910307

Phase: Not Applicable

Status: Recruiting

Eligibility: Individuals diagnosed with synovial sarcoma, treated in the United States.

Overview: This study aims to establish a registry and biorepository for synovial sarcoma patients by collecting and storing data and biospecimens to further research and improve outcomes. This study is funded by the Synovial Sarcoma Foundation.​

More Information: https://www.research.chop.edu/synovial-sarcoma-registry-biospecimen-repository ​

Treatment Centers:

• Children's Hospital of Philadelphia (CHOP), Philadelphia, PA, USA​
• This registry is open to anyone treated in the United States; participation does not require travel to Philadelphia.

Trial ID: NCT04673942 (BETA-PRIME study)

Phase: 1/2

Status: Recruiting

Eligibility: Adults aged 18 and older with advanced synovial sarcoma that has not responded to standard treatments. Patients must have injectable tumors and good organ function.​

Overview: This study tests AdAPT-001, a virus-based therapy designed to attack cancer cells and boost the immune system. The virus is injected into tumors to trigger an immune response. Some patients also receive a PD-1/L1 checkpoint inhibitor to enhance the effect.​

Preliminary Effectiveness: Early results show that 21% of patients had tumor shrinkage, and 38% had no disease progression for at least six months. Side effects were mostly mild, such as flu-like symptoms and injection pain. The FDA has given Fast Track status to this treatment.​

More Information: https://clinicaltrials.gov/ct2/show/NCT04673942

Treatment Centers:

• MD Anderson Cancer Center, TX, USA​
• Washington University, MO, USA​
• City of Hope, CA, USA​
• Mayo Clinic, MN, USA​
• Dana-Farber Cancer Institute, MA, USA​
• University of Chicago, IL, USA

Trial ID: NCT05642455

Phase: 1/2
Status: Recruiting

Eligibility:
Children and young adults aged 2–21 years with metastatic or unresectable synovial sarcoma (or select pediatric tumors) that are HLA-A*02 positive and express MAGE-A4. Participants must weigh ≥10 kg and have received prior chemotherapy. Good performance status (ECOG 0–1 or Lansky Score ≥80) is required.

Overview:
This study expands the FDA-approved afamitresgene autoleucel (afami-cel, Tecelra) TCR-T therapy to pediatric patients. Afami-cel modifies a patient’s own T-cells to express a T-cell receptor (TCR) targeting MAGE-A4, a protein commonly found in synovial sarcoma. The trial is a multi-center “basket” study, meaning all participants receive afami-cel after chemotherapy, but results are tracked separately for each cancer type.

For synovial sarcoma patients under 21, the study aims to evaluate safety (Phase 1) and anti-tumor activity (Phase 2) of afami-cel in a younger population. The process mirrors adult treatment: T-cells are harvested, genetically modified to recognize MAGE-A4, expanded, and infused back into the patient. The trial monitors tumor responses, potential side effects, and long-term survival.

Preliminary Effectiveness:
In adult clinical trials, afami-cel achieved a 39% response rate in advanced synovial sarcoma, leading to its FDA approval. Pediatric data is still emerging, but this study aims to determine whether similar efficacy extends to younger patients. The hope is that afami-cel will improve survival rates, as pediatric synovial sarcoma currently has limited options beyond chemotherapy. Early case reports are promising, and the study will formally assess tumor response rates and two-year relapse rates.

More Information:
https://clinicaltrials.gov/study/NCT05642455

Treatment Centers:

• Children’s Hospital of Philadelphia (CHOP), PA, USA
• MSK (Pediatrics), NY, USA
• Stanford Children’s Health, CA, USA
• Cincinnati Children’s Hospital, OH, USA
• NIH Clinical Center, MD, USA
• Additional SARC Consortium Sites (US & Canada, with possible expansion to Europe/Australia)

Trial ID: NCT04589754

Phase: 2

Status: Recruiting

Eligibility: Patients aged 14 to 70 with advanced synovial sarcoma that has not responded to standard treatments. Participants must have at least one measurable tumor lesion and good performance status (ECOG 0–1).​

Overview: This study evaluates whether adding sintilimab, a PD-1 checkpoint inhibitor, to standard chemotherapy (doxorubicin and ifosfamide) improves outcomes in advanced synovial sarcoma. The trial compares the combination therapy to chemotherapy alone, assessing tumor response rates, progression-free survival, and safety.​

Preliminary Effectiveness: Effectiveness data is not yet available.​

More Information: https://clinicaltrials.gov/ct2/show/NCT04589754

Treatment Centers:

• Sun Yat-sen University Cancer Center, Guangzhou, China​
• Henan Cancer Hospital, Zhengzhou, China​
• Fudan University Shanghai Cancer Center, Shanghai, China​
• Peking University Cancer Hospital, Beijing, China​
• West China Hospital, Sichuan University, Chengdu, China

Trial ID: NCT03132922

Phase: 1

Status: Active, Not Recruiting

Eligibility: Adults with advanced synovial sarcoma expressing the MAGE-A4 antigen and positive for HLA-A*02. Participants must have measurable disease and have progressed after prior standard therapies.

Overview: This Phase 1 trial evaluated the safety and preliminary efficacy of ADP-A2M4, an investigational therapy where patients' own T-cells are genetically modified to express a T-cell receptor targeting the MAGE-A4 antigen. Following lymphodepleting chemotherapy, these engineered T-cells were infused back into the patient to specifically recognize and attack MAGE-A4–positive tumor cells. The study aimed to determine the safety profile, appropriate dosing, and early signs of efficacy of this novel T-cell therapy in patients with advanced synovial sarcoma.

Preliminary Effectiveness: Initial results demonstrated an overall response rate of approximately 39%, with some patients experiencing significant tumor shrinkage and disease stabilization. Responses lasted a median of approximately 12 months, indicating potential durable benefits in this patient population.

More Information: https://clinicaltrials.gov/ct2/show/NCT03132922

Treatment Centers:

• MD Anderson Cancer Center, Houston, TX, USA
• National Institutes of Health Clinical Center, Bethesda, MD, USA
• University of California, Los Angeles (UCLA), Los Angeles, CA, USA
• Fred Hutchinson Cancer Research Center, Seattle, WA, USA
• H. Lee Moffitt Cancer Center, Tampa, FL, USA
• Massachusetts General Hospital, Boston, MA, USA
• Memorial Sloan Kettering Cancer Center, New York, NY, USA
• City of Hope Comprehensive Cancer Center, Duarte, CA, USA
• University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA

Trial ID: NCT03967223

Phase: 2

Status: Active, Not Recruiting

Eligibility: Individuals aged 10 years and older with unresectable or metastatic synovial sarcoma (SyS) or myxoid/round cell liposarcoma (MRCLS) expressing the NY-ESO-1 antigen. Participants must be positive for HLA-A02:01, HLA-A02:05, or HLA-A*02:06 alleles and have previously received anthracycline-based chemotherapy.​

Overview: This Phase 2 study evaluates the safety and efficacy of letetresgene autoleucel (lete-cel), an investigational T-cell receptor (TCR) therapy targeting the NY-ESO-1 antigen, in patients with advanced SyS or MRCLS. Lete-cel involves engineering patients' own T-cells to recognize and attack tumor cells expressing NY-ESO-1. Participants undergo lymphodepleting chemotherapy followed by infusion of the modified T-cells. The trial aims to determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and safety profile of lete-cel in this patient population. ​

Preliminary Effectiveness: As of the latest interim analysis, lete-cel demonstrated an ORR of 42% among 64 evaluable patients, with 6 complete responses and 21 partial responses. The median DOR was 12.2 months, and the median PFS was 5.3 months. These results indicate promising anti-tumor activity in heavily pretreated patients with SyS and MRCLS. ​

More Information: https://clinicaltrials.gov/ct2/show/NCT03967223

Treatment Centers:

United States
City of Hope, CA, USA
Stanford Health Care, CA, USA
Sarah Cannon, CO, USA
Mayo Clinic, FL, USA
University of Chicago, IL, USA
University of Iowa, IA, USA
Dana-Farber, MA, USA
Mass General, MA, USA
University of Michigan, MI, USA
Minnesota Oncology, MN, USA
Mayo Clinic, MN, USA
Washington University, MO, USA
MSK, NY, USA
Duke University, NC, USA
OSU (Wexner), OH, USA
OHSU, OR, USA
UPMC Hillman, PA, USA
Sarah Cannon, TN, USA
UT Southwestern, TX, USA
University of Utah, UT, USA
VCU, VA, USA
Fred Hutch, WA, USA
Froedtert, WI, USA

Canada
Princess Margaret, Toronto, Canada
CIUSSS de l'Est, Montreal, Canada

France
Centre Léon Bérard, Lyon, France
CHU de Bordeaux, Pessac, France

Italy
Istituto Nazionale Tumori, Milan, Italy
Istituto Clinico Humanitas, Rozzano, Italy

Netherlands
Netherlands Cancer Institute, Amsterdam, Netherlands

Spain
Hospital Santa Creu i Sant Pau, Barcelona, Spain
ICO Duran i Reynals, Barcelona, Spain
Fundación Jiménez Díaz, Madrid, Spain
Hospital Virgen del Rocío, Seville, Spain

United Kingdom
Royal Marsden, London, UK
University College Hospital, London, UK
Christie Hospital, Manchester, UK

Phase: 2

Status: Active, Not Recruiting

Eligibility: Adults with unresectable or metastatic synovial sarcoma expressing MAGE-A4 antigen who previously received chemotherapy and are positive for HLA-A02:01P, -A02:02P, -A02:03P, or -A02:06P.

Overview: This ongoing study evaluates Tecelra (afamitresgene autoleucel), an FDA-approved treatment using patients' own genetically modified T-cells to target and destroy synovial sarcoma cells expressing the MAGE-A4 antigen. Patients first undergo chemotherapy to prepare the body for treatment, after which their genetically modified T-cells are infused back into their bloodstream to specifically attack the cancer cells. While initial approval was based on early results, this continuing study aims to confirm long-term effectiveness, safety, and potential side effects, fulfilling requirements set by the FDA for treatments granted accelerated approval.

Preliminary Effectiveness: Clinical trials leading to FDA accelerated approval showed a 39% overall response rate, with responses lasting a median of approximately 12 months. Patients experienced significant tumor shrinkage and sustained disease stabilization where prior therapies had failed.

More Information: https://clinicaltrials.gov/study/NCT04044768

Treatment Centers:

• MSK, NY, USA
• MD Anderson, TX, USA
• Moffitt Cancer Center, FL, USA
• Mayo Clinic, MN, USA
• Stanford Cancer Institute, CA, USA
• Stanford Health Care, CA, USA
• City of Hope, CA, USA
• Northwestern Memorial, IL, USA
• Penn Medicine, PA, USA
• Hospital of the University of Pennsylvania, PA, USA
• Dana-Farber, MA, USA
• Mass General, MA, USA
• OSU (Wexner), OH, USA
• Cleveland Clinic, OH, USA
• Vanderbilt-Ingram, TN, USA
• Vanderbilt University Medical Center, TN, USA
• Duke University Hospital, NC, USA
• Fred Hutch, WA, USA
• Princess Margaret Cancer Centre, Toronto, Canada
• Institut Bergonié, Bordeaux, France
• Gustave Roussy, Villejuif, France
• Istituto Nazionale Tumori, Milan, Italy
• Royal Marsden Hospital, London, UK
• University Hospital Heidelberg, Heidelberg, Germany
• Vall d’Hebron Institute of Oncology, Barcelona, Spain

Trial ID: Pending registration; IND approved – Medigene’s EPITOME-1015-I Study​

Phase: 1 (dose escalation & expansion)​

Status: Not yet recruiting (expected to start in 2025)​

Eligibility: Adults with advanced synovial sarcoma, myxoid/round cell liposarcoma, gastric cancer, or ovarian cancer expressing NY-ESO-1/LAGE-1a and positive for HLA-A*02. Patients must have relapsed or refractory disease after standard treatments.

Overview: This upcoming trial will evaluate MDG1015, a third-generation TCR-T therapy targeting NY-ESO-1/LAGE-1a. MDG1015 utilizes patients' T-cells engineered with an affinity-optimized T-cell receptor (TCR) specific to NY-ESO-1/LAGE-1a and incorporates a PD1-41BB costimulatory switch protein designed to enhance T-cell activity by overcoming immunosuppressive PD-1 signals within the tumor microenvironment. The study will commence with dose escalation to assess safety and determine the optimal dose, followed by an expansion phase to preliminarily evaluate tumor responses in NY-ESO-1/LAGE-1a positive cancers. Researchers will monitor T-cell persistence, anti-tumor activity, and potential side effects.​

Preliminary Effectiveness: Preclinical studies have demonstrated potent tumor-killing activity by MDG1015 T-cells, including against tumors with high PD-L1 expression, and improved T-cell fitness due to a streamlined 6-day manufacturing process. These findings, along with the efficacy observed in earlier NY-ESO-1-targeted TCR-T therapies, suggest MDG1015 could induce strong anti-tumor responses.​

More Information: https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00213 ​

Treatment Centers: The trial is planned to launch in the United States and Europe, with anticipated sites at major cancer centers (specific locations to be determined as the study opens).