Ongoing Clinical Trials for Synovial Sarcoma

Seven clinical trials are currently underway across Europe investigating various treatment approaches for synovial sarcoma, a rare cancer that typically occurs near the joints. These studies include innovative cell therapies, personalized vaccines, and targeted immunotherapies, with trials taking place in multiple European countries including Germany, France, Spain, Italy, the Netherlands, Belgium, Poland, Austria, and Ireland.

Clinical trial locations

• Austria
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
• Belgium
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
• France
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Letetresgene Autoleucel for Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
  • Study of Afamitresgene Autoleucel for Patients with Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
  • Study of Long-term Safety of Tazemetostat in Patients Who Previously Participated in Tazemetostat Clinical Trials
• Germany
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Personalized Peptide Vaccine with PERVI-FUS, PERVI-NEO, and 11902A for Children and Young Adults with Metastatic Fusion-Driven Sarcomas
  • Study of Trabectedin alone versus Trabectedin with tTF-NGR combination therapy in adults with metastatic or refractory soft tissue sarcoma who failed first-line treatment
• Ireland
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
• Italy
  • Long-Term Follow-Up Study for Patients with Myxoid/Round Cell Liposarcoma, Multiple Myeloma, Non-Small Cell Lung Cancer, or Synovial Sarcoma Treated with Letetresgene Autoleucel
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Letetresgene Autoleucel for Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
• Netherlands
  • Long-Term Follow-Up Study for Patients with Myxoid/Round Cell Liposarcoma, Multiple Myeloma, Non-Small Cell Lung Cancer, or Synovial Sarcoma Treated with Letetresgene Autoleucel
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Letetresgene Autoleucel for Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
• Poland
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Long-term Safety of Tazemetostat in Patients Who Previously Participated in Tazemetostat Clinical Trials
• Spain
  • Long-Term Follow-Up Study for Patients with Myxoid/Round Cell Liposarcoma, Multiple Myeloma, Non-Small Cell Lung Cancer, or Synovial Sarcoma Treated with Letetresgene Autoleucel
  • Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01
  • Study of Letetresgene Autoleucel for Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma
  • Study of Afamitresgene Autoleucel for Patients with Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

Long-Term Follow-Up Study for Patients with Myxoid/Round Cell Liposarcoma, Multiple Myeloma, Non-Small Cell Lung Cancer, or Synovial Sarcoma Treated with Letetresgene Autoleucel

This long-term safety monitoring study tracks patients who have previously received letetresgene autoleucel, an adoptive cell therapy treatment. The study focuses on observing potential delayed side effects following treatment with genetically modified immune cells.

Main inclusion criteria: Participants must have received at least one infusion of adoptive cell therapy in a previous study and must have completed or withdrawn from that earlier trial. Both male and female participants are eligible. Male participants must use contraception for at least 12 months after receiving the cell therapy, or until gene-modified cells are no longer detectable. Women of childbearing potential must use effective contraception for the same period. Participants must be able to provide informed consent, and for those under 18, a legal guardian must provide consent.

Main exclusion criteria: Despite being a synovial sarcoma study, the exclusion criteria oddly state that patients with synovial sarcoma cannot participate, which appears to be an error in the source data.

Focus and goal: The primary aim is to monitor participants for any delayed adverse effects from the genetically modified cell therapy, including new cancers, neurological disorders, autoimmune conditions, blood disorders, or infections. Blood samples are collected regularly to track specific DNA markers and the presence of modified cells in the body. The study continues until 2032, providing comprehensive long-term safety data.

Investigational treatment: The study monitors patients who have received adoptive cell therapy, specifically GSK3377794, which involves genetically modified immune cells designed to help the body target and destroy cancer cells more effectively.

Study of IMC-F106C alone and with checkpoint inhibitors in patients with advanced PRAME-positive cancers who have HLA-A*02:01

This two-phase study evaluates IMC-F106C (brenetafusp) in treating advanced PRAME-positive cancers in patients with a specific genetic marker. The treatment is tested both alone and combined with other cancer medications including pembrolizumab and various chemotherapy drugs.

Main inclusion criteria: Participants must be 18 years or older with an ECOG performance status of 0 or 1, meaning they can perform daily activities with minimal assistance. They must test positive for both HLA-A*02:01 and have PRAME-positive tumors. Participants should have cancer that returned after previous treatment, did not respond to standard treatments, or be unable to tolerate standard treatments.

Main exclusion criteria: Prior treatment with PRAME-targeted therapy is not allowed. Patients with active or untreated brain metastases, severe heart problems, uncontrolled infections, HIV, Hepatitis B or C infections, pregnancy, or breastfeeding cannot participate. Major surgery within 4 weeks before the study or participation in another trial within the same timeframe also excludes patients.

Focus and goal: Phase 1 determines the safest and most effective dose of IMC-F106C delivered through intravenous or subcutaneous injection. Phase 2 evaluates how well the treatment works in specific types of advanced solid tumors. Researchers monitor side effects and measure cancer responses throughout the study, which continues until April 2029.

Investigational treatment: IMC-F106C is a novel immunotherapy designed to target PRAME-positive cancers. It can be given either into the vein or under the skin. Checkpoint inhibitors are also used in combination to help the immune system recognize and attack cancer cells more effectively.

Study of Letetresgene Autoleucel for Patients with Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

This study specifically focuses on two rare soft tissue cancers: synovial sarcoma and myxoid/round cell liposarcoma. The treatment uses the patient’s own immune cells, modified in a laboratory to better recognize and attack cancer cells.

Main inclusion criteria: Participants must be at least 10 years old, with children requiring guardian permission. Patients must have confirmed diagnosis of synovial sarcoma or myxoid/round cell liposarcoma that has spread or cannot be removed surgically. The cancer must show specific genetic changes called translocations and test positive for the NY-ESO-1 protein in at least 30% of tumor cells. Participants must test positive for specific genetic markers (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06). They should have received at least one standard treatment and have adequate heart function and physical ability.

Main exclusion criteria: Patients whose tumors lack the NY-ESO-1 and/or LAGE-1a markers or do not have the required HLA genetic markers cannot participate.

Focus and goal: The study evaluates how effective and safe this personalized cell therapy is. The process involves collecting white blood cells through leukapheresis, modifying them to target specific cancer proteins, and then infusing them back into the patient. Regular monitoring assesses treatment effectiveness and any side effects. The study is expected to conclude by March 2025.

Investigational treatment: GSK3377794 consists of NY-ESO-1-specific T cells that are genetically engineered to recognize and attack cancer cells expressing specific proteins. These modified cells are administered through a one-time intravenous infusion, sometimes in combination with other anti-cancer agents.

Study of Personalized Peptide Vaccine with PERVI-FUS, PERVI-NEO, and 11902A for Children and Young Adults with Metastatic Fusion-Driven Sarcomas

This specialized study focuses on children and young adults with fusion-driven sarcomas that have spread to other body parts. It tests a personalized vaccine designed to boost the immune system’s response to cancer.

Main inclusion criteria: Patients must have fusion-driven metastatic sarcoma, including Ewing sarcoma, alveolar rhabdomyosarcoma, or synovial sarcoma. They should be in first or second complete remission or partial response after completing local therapy and intensive chemotherapy. Specific genetic information from whole exome and RNA sequencing must be available, and a personalized vaccine must have been successfully created. Both male and female patients in the specified age range can participate.

Main exclusion criteria: Patients without fusion-driven metastatic sarcoma or those not in the required remission stage cannot participate. Patients outside the specified age range or those not meeting vulnerable population criteria are also excluded.

Focus and goal: The study aims to determine if the personalized IPX vaccine can successfully induce a T-cell immune response without causing unacceptable side effects. The vaccine is made up of specific proteins including PERVI-FUS, PERVI-NEO, and 11902A. Treatment continues for a maximum of 113 days, with follow-up visits to monitor immune response, overall health, and quality of life. The final assessment occurs 180 days after starting the study.

Investigational treatment: The individualized peptide vaccine is specifically tailored for each patient based on their unique cancer characteristics. It is designed to help the immune system recognize and attack cancer cells using small proteins that match the patient’s specific tumor profile.

Study of Trabectedin alone versus Trabectedin with tTF-NGR combination therapy in adults with metastatic or refractory soft tissue sarcoma who failed first-line treatment

This comparative study tests whether adding an experimental drug to standard chemotherapy improves outcomes for patients with soft tissue sarcomas that have spread or not responded to initial treatments.

Main inclusion criteria: Participants must be between 18 and 75 years old with advanced or metastatic high-grade soft tissue sarcoma (grade 2-3), including synovial sarcoma. They must have disease that did not respond to previous anthracycline treatment or cannot take anthracyclines for medical reasons. Tumors must test positive for CD13 with a score of 1 or higher and have at least one measurable tumor not previously treated with radiation. Patients must have a life expectancy of at least 3 months and an ECOG Performance Status of 2 or less.

Main exclusion criteria: People outside the age range of 18-75, those without confirmed soft tissue sarcoma, those with negative CD13 test results, pregnant or breastfeeding women, patients with severe heart, liver, or kidney problems, active uncontrolled infections, or other active cancers requiring treatment cannot participate.

Focus and goal: The study compares trabectedin alone to trabectedin combined with tTF-NGR. The experimental drug is designed to concentrate chemotherapy inside the tumor. Participants are randomly assigned to receive either trabectedin alone or the combination. Treatment continues for up to 360 days, with regular medical examinations and imaging tests to monitor response. The study runs until March 2029.

Investigational treatment: Trabectedin is a chemotherapy medication given through intravenous infusion. tTF-NGR is an experimental protein therapy designed to target blood vessels in tumors and trap the chemotherapy medication inside the tumor, potentially making treatment more effective.

Study of Afamitresgene Autoleucel for Patients with Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

This advanced cell therapy study evaluates a treatment where patients’ own immune cells are genetically modified to target and fight cancer cells.

Main inclusion criteria: Patients must be between 16 and 75 years old with confirmed diagnosis of advanced synovial sarcoma or myxoid liposarcoma that has spread or cannot be surgically removed. They must have received previous treatment containing anthracycline or ifosfamide. The tumor must show at least 30% expression of MAGE-A4 protein, and patients must test positive for HLA-A*02 genetic markers. Adequate heart function (LVEF 50% or higher) and suitable veins for blood cell collection are required. ECOG Performance Status must be 0 or 1. Both men and women must agree to use effective birth control.

Main exclusion criteria: Patients without the specified cancer types, those not HLA-A*02 positive, those whose cancer does not express MAGE-A4, patients outside the age range, or those considered part of vulnerable populations cannot participate.

Focus and goal: The treatment process involves collecting white blood cells through leukapheresis, genetically modifying them in a laboratory to create ADP-A2M4 SPEAR T cells that target MAGE-A4-expressing cancer cells, and then infusing these modified cells back into the patient. Before the infusion, patients receive a short course of chemotherapy to prepare their immune system. Close monitoring follows the infusion to assess effectiveness and safety, with long-term follow-up extending over time.

Investigational treatment: Afamitresgene autoleucel consists of genetically modified T cells (ADP-A2M4 SPEAR T cells) taken from the patient’s own body. These cells are altered to better recognize and attack cancer cells that express the MAGE-A4 protein, representing a personalized immunotherapy approach.

Study of Long-term Safety of Tazemetostat in Patients Who Previously Participated in Tazemetostat Clinical Trials

This long-term safety monitoring study follows patients who previously benefited from tazemetostat treatment in earlier clinical trials.

Main inclusion criteria: Participants must be currently benefiting from tazemetostat treatment either alone or in combination with other medications. They must have a life expectancy of more than 3 months and show adequate blood cell counts, bone marrow function, kidney function, and liver function. Women of childbearing potential need a negative pregnancy test and must use both highly effective birth control and barrier methods during treatment and for 6 months after. Men must either have had a vasectomy and use condoms, or both partners must use effective contraception during treatment and for 3 months after the last dose.

Main exclusion criteria: Patients not currently receiving tazemetostat, those who experienced severe side effects during previous treatment, those unable to comply with monitoring requirements, those who developed medical conditions making continued treatment unsafe, or those who withdrew consent from previous studies cannot participate. Patients with progressive disease while on treatment or participating in other trials simultaneously are also excluded.

Focus and goal: The study monitors long-term safety in patients continuing tazemetostat treatment. Researchers track side effects, treatment tolerance, blood cell counts, kidney function, liver function, and survival while patients receive the medication according to their previous treatment plan. The study continues until September 2025.

Investigational treatment: Tazemetostat is an oral medication in tablet form that belongs to a class of drugs called EZH2 inhibitors. These medications work by blocking specific enzymes in cancer cells, helping to control the growth of certain types of cancer.

Summary

The seven ongoing clinical trials for synovial sarcoma reflect a strong focus on innovative immunotherapy approaches, particularly cell-based therapies. Three trials specifically test adoptive cell therapy treatments where patients’ own immune cells are genetically modified to target cancer cells. These personalized treatments represent cutting-edge approaches in cancer medicine.

Geographically, the trials are concentrated in Western European countries, with France, Spain, Italy, the Netherlands, and Germany hosting multiple studies. This concentration suggests these countries have established expertise and infrastructure for advanced cancer treatment research. Belgium, Austria, Ireland, and Poland also participate in some trials, indicating growing regional collaboration in rare cancer research.

The studies predominantly target patients whose cancer has advanced or spread despite previous treatments, addressing a significant unmet medical need. Most trials require specific genetic markers for participation, highlighting the move toward precision medicine where treatments are tailored to individual genetic profiles. Several trials include both synovial sarcoma and myxoid/round cell liposarcoma, recognizing similarities in how these rare cancers can be treated.

One notable trial focuses specifically on children and young adults with metastatic disease, reflecting the fact that synovial sarcoma often affects younger people. The long-term follow-up studies demonstrate commitment to understanding not just immediate treatment effects but also long-term safety over many years.