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)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- USWM CT, LLC
- 入组人数
- 103
- 试验地点
- 38
- 主要终点
- Substudy 1: Overall response rate (ORR)
研究概览
简要总结
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.
详细描述
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells. This is a master protocol investigating T-cell therapies. It will initially consist of a core protocol with two independent substudies investigating Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This will be an open-label study. Hence, there will be no masking.
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be greater than or equal to 10 years of age on the day of signing informed consent.
- •Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg
- •Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a designated central laboratory
- •Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
- •Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)
- •Performance status: dependent on age - Lansky > 60, Karnofsky > 60, Eastern Cooperative Oncology Group 0-
- •Participant must have adequate organ function and blood cell counts, within 7 days prior to leukapheresis.
- •At time of treatment, participant has measurable disease according to RECIST v1.
- •Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
- •Consultation for prior history per protocol specifications.
排除标准
- •Central nervous system metastases.
- •Any other prior malignancy that is not in complete remission.
- •Clinically significant systemic illness (Serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the participant's ability to tolerate protocol therapy or significantly increase the risk of complications).
- •Prior or active demyelinating disease.
- •History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring steroids or other immunosuppressive treatments.
- •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.
- •Previous allogeneic hematopoietic stem cell transplant.
- •Washout periods for prior radiotherapy and systemic chemotherapy must be followed.
- •Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
- •Prior radiation exceeds protocol specified limits.
研究组 & 干预措施
Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Fludarabine (Drug)
Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Cyclophosphamide (Drug)
Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Letetresgene autoleucel (lete-cel, GSK3377794) (Drug)
Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Letetresgene autoleucel (lete-cel, GSK3377794) (Drug)
Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Fludarabine (Drug)
Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo
Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Substudy 1: Overall response rate (ORR)
时间窗: Until disease progression (up to 5 years)
Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants within the analysis population at any time per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. as determined by the local investigators.
Substudy 2: Overall response rate (ORR) as assessed by central independent review
时间窗: Up to 5 years
Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as assessed by central independent review.
次要结局
- Substudy 1 and 2: Time to response (TTR)(Until disease progression (up to 5 years))
- Substudy 1 and 2: Duration of response (DOR)(Until disease progression (up to 5 years))
- Substudy 1 and 2: Disease control rate (DCR)(Until disease progression (up to 5 years))
- Substudy 1 and 2: Progression free survival (PFS)(Until disease progression (up to 5 years))
- Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel(Until disease progression (up to 5 years))
- Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel(Until disease progression (up to 5 years))
- Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity(Until disease progression (up to 5 years))
- Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)(Until disease progression (up to 5 years))
- Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel(Until disease progression (up to 5 years))
- Substudy 2: Overall Survival (OS)(Up to 5 years)
- Substudy 2: Overall response rate (ORR) as determined by the local investigators(Up to 5 years)
- Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel(Up to 36 months)
- Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)(Until disease progression (up to 5 years))
- Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters(Until disease progression (up to 5 years))