synovial sarcoma or myxoid/roundcell liposarcoma
Conditions
Interventions
Treatment with GSK3377794 with or without other anti-cancer agents.
Sub study 1 and 2: GSK3377794.
Sponsors
Adaptimmune LLC
Eligibility
Age
16 Years to 99 Years
Inclusion criteria
Inclusion criteria: SUBSTUDY 1: SCREENING: • Male or female, in NL age 16 years and above (protocol: 10 years and above). • Body Weight of at least 40kg. For weight =1 year after adjuvant/neoadjuvant therapy for localized disease. • Contraception requirements apply at the time of leukapheresis and treatment. • Representative tumor sample (archived or fresh) for NY-ESO-1 analysis. See protocol section 6.1, item 7. LEUKAPHERESIS: • Life expectancy >=24 weeks • Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. • HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and meeting the threshold for expression of NY-ESO-1 (>=30% of cells that are 2+ or 3+ by immunohistochemistry). • Left ventricular ejection fraction >=45%. • ECOG performance status 0-1. • Adequate organ function, see protocol chapter 6.1 Table 5. • Fit for leukapheresis and adequate venous access for leukapheresis. • Contraception guidelines for males and females should be followed, see chapter 6.1, item 14 of the protocol for details. • Negative pregnancy test for female participants able to become pregnant. CHEMOTHERAPY/TREATMENT: • Measurable disease (RESIST 1.1). • Supportive radiotherapy has not affected >25% of bone marrow. • A biopsy of non-target tumor tissue obtained within 28 days prior to initiating the chemotherapy is mandatory. SUBSTUDY 2: SCREENING: • Male or female, in NL age 16 years and above (protocol: 10 years and above). • Diagnosis of synovial sarcoma or myxoid/round cell liposarcoma confirmed by local histopathology and with evidence of disease-specific translocation as mentioned in chapter 6.1, item 3 of the protocol. • High risk locally advanced or advanced synovial sarcoma or myxoid/round cell liposarcoma. See protocol section 6.1, item 4 for details. • Currently being treated with or has completed at least one standard of care treatment including anthracycline or anthracycline with ifosfamide for advanced (metastatic or inoperable) disease. See protocol section 6.1, item 5 for details. • Contraception requirements apply at the time of leukapheresis and treatment. • Archival sample from most recent biopsy or fresh biopsy of tumor tissue is available for NY-ESO-1 analysis. LEUKAPHERESIS: • Successfully completed screening: HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and meeting the threshold for expression of NY-ESO-1 (>=30% of cells that are 2+ or 3+ by immunohistochemistry). • Left ventricular ejection fraction >=45%. • ECOG performance status 0-1. • Adequate organ function (see protocol Table 4). • Fit for leukapheresis and adequate venous access for leukapheresis. • Contraception guidelines for males and females should be followed, see chapter 6.1, item 14 of the
Exclusion criteria
Exclusion criteria: SUBSTUDY 1: SCREENING: • Previously treated for metastatic synovial sarcoma. • CNS metastases. • Previous treatment with genetically engineered NY-ESO-1-specific T cells. • Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. • Prior gene therapy using an integrating vector. • Prior allogeneic hematopoietic stem cell transplant. • Clinically significant systemic illness, see protocol section 6.2, item 8 for details. LEUKAPHERESIS: • History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. • Uncontrolled intercurrent illness. See protocol chapter 6.2, item 10 for details. • Current active liver or biliary disease. See protocol chapter 6.2, item 11 for details. • QTc >480 msec. See protocol chapter 6.2, item 12 for details. • Investigational treatment within 30 days or 5 half-lives (whichever is shorter). • Active infections. See protocol chapter 6.2, item 17 for details. CHEMOTHERAPY/TREATMENT: • Cytotoxic therapy within the last 3 weeks. • Systemic corticosteroids or any other immunosuppressive therapy within the last 2 weeks. • Participant has received >=50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the Investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion. • Anti-cancer vaccine within the last 2 months in the absence of tumor response. See protocol chapter 6.2, item 22 for details. • Live vaccine within the last 4 weeks prior to lymphodepletion or intends to receive live vaccine during the 3 month period following administration of GSK3377794. • Immune therapy within the last 4 weeks. See protocol chapter 6.2, item 24 for details. • Washout periods for prior therapy see protocol chapter 6.2, Table 5. SUBSTUDY 2: SCREENING: • CNS metastases. • Previous treatment with genetically engineered NY-ESO-1-specific T cells. • Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. • Prior gene therapy using an integrating vector. • Prior allogeneic hematopoietic stem cell transplant. • Clinically significant systemic illness, see protocol section 6.2, item 7 for details. LEUKAPHERESIS: • History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. • Uncontrolled intercurrent illness. See protocol chapter 6.2, item 9 for details. • Current active liver or biliary disease. See protocol chapter 6.2, item 10 for details. • QTc >480 msec. See protocol chapter 6.2, item 11 for details. • Investigational treatment within 30 days or 5 half-lives (whichever is shorter). • Active infections. See protocol chapter 6.2, item 16 for details. CHEMOTHERAPY/TREATMENT: • Cytotoxic therapy within the last 3 weeks. • Systemic corticosteroids or any other immunosuppressive therapy within the last 2 weeks. • Participant has received >=50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the Investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion. • Anti-cancer vaccine within the last 2 months in the absenc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR) (RECIST 1.1). | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival (PFS). Disease Control Rate (DCR). Duration of Response (DoR). Time to Response (TTR). Overall survival (OS). Adverse events. Replication Competent Lentivirus. T cell Persistence. Insertional oncogenesis. | — |
Countries
Netherlands
Outcome results
None listed