A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
研究概览
简要总结
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
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 (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is greater than equal to (>=)18 years of age at the time of signing the study informed consent.
- •Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12).
- •Participant has measurable disease according to RECIST v1.1 criteria.
- •Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
- •Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
- •Participant must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
- •Participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for NY-ESO-1 expression by a designated central laboratory.
- •Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Participant has a left ventricular ejection fraction >=45%.
- •Participant is fit for apheresis and has adequate venous access for the cell collection.
- •Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.
排除标准
- •Any previous gene therapy using an integrating vector.
- •Any previous allogeneic hematopoietic stem cell transplant.
- •Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
- •Participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
- •Participant has known active brain or leptomeningeal metastases.
- •Participant has other prior malignancy that is not in complete remission.
- •Participant has uncontrolled intercurrent illness including, but not limited to:
- •(i) Ongoing or active infection.
- •(ii) Clinically significant cardiac disease
- •(iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
- •Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).
研究组 & 干预措施
letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
干预措施: letetresgene autoleucel (GSK3377794) (Drug)
letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
干预措施: Cyclophosphamide (Drug)
letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
干预措施: Fludarabine (Drug)
结局指标
主要结局
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
时间窗: Up to 24 months
Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
时间窗: Up to 24 months
The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response \[CR\] \> Confirmed Partial Response \[PR\] \> Stable Disease \[SD\] \> Progressive Disease \[PD\] \> Not Evaluable \[NE\]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST v1.1 Criteria.
次要结局
- Time to Response (TTR) Assessed by Investigator(Up to 24 months)
- Duration of Response (DOR) Assessed by Investigator(Up to 24 months)
- Progression Free Survival (PFS) Assessed by Investigator(Up to 24 months)
- Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs(Up to 24 months)
- Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline(Up to 24 months)
- Number of Participants With Positive Anti-drug Antibodies (ADAs)(Up to 24 Months)
- Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment(Up to 24 months)
- Number of Participants With Adverse Event of Special Interest (AESI)(Up to 24 months)
- Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline(Up to 24 months)
- Number of Participants With Insertional Oncogenesis(Up to 2 years)
- Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer(Up to 24 months)
- Time to Response (TTR) Assessed by Independent Reviewer(Up to 24 months)
- Progression Free Survival (PFS) Assessed by Independent Reviewer(Up to 24 months)
- Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794(Up to 28 days)
- Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval(Baseline, Day 1, Day 4 and Day 8)
- Change From Baseline in ECG Mean Heart Rate(Baseline, Day 1 (Pre-dose), Day 4 and Day 8)
- Time to Cmax (Tmax)(Day 2 to Day 15)
- Duration of Response (DOR) Assessed by Independent Reviewer(Up to 24 months)
- Number of Participants With Replication Competent Lentivirus (RCL)(Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion)
- Maximum Transgene Expansion (Cmax) of GSK3377794(Day 2 to Day 15)