Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, alone or in combination with other agents, in HLA-A2+ Participants with NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO) (study 208467)
- Conditions
- synovial sarcoma or myxoid/roundcell liposarcomasarcoma10072990
- Registration Number
- NL-OMON52674
- Lead Sponsor
- Adaptimmune LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 6
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 <40 kg: consult medical monitor
first.
• 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.
• Synovial sarcoma or round cell liposarcoma that is newly diagnosed,
previously untreated OR
relapsed after surgery or radiotherapy for localized disease OR relapsed >=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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Response Rate (ORR) (RECIST 1.1).</p><br>
- Secondary Outcome Measures
Name Time Method <p>Progression-Free Survival (PFS). Disease Control Rate (DCR). Duration of<br /><br>Response (DoR). Time to Response (TTR). Overall survival (OS). Adverse events.<br /><br>Replication Competent Lentivirus. T cell Persistence. Insertional oncogenesis.</p><br>