NCT04044768进行中（未招募）2 期
A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
适应症
干预措施
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
- 52
- 试验地点
- 26
- 主要终点
- Overall Response Rate (ORR) (Cohort 1)
研究概览
简要总结
This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .
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
- 10 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥16 (10 years at selected sites) and <=75 years
- •Diagnosis of advanced synovial sarcoma (Cohort 1, Cohort 2 and Cohort 3) or myxoid liposarcoma / myxoid round cell liposarcoma (Cohort 1 only) confirmed by cytogenetics.
- •Previously received either an anthracycline or ifosfamide containing regimen.
- •Measurable disease according to RECIST v1.1 prior to lymphodepletion
- •HLA-A*02:01, HLA-A*02:02, HLA-A*02:03 or HLA-A*02:06 positive
- •Tumor shows MAGE-A4 expression confirmed by central laboratory. North America Only (United States and Canada): Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of ≥1+ staining in ≥10% of the cells by immunohistochemistry.
- •ECOG Performance Status of 0 or
- •For subjects aged ≥10 to ≥16 years old:
- •Lansky Score ≥60%.
- •Left ventricular ejection fraction (LVEF) ≥50%.
- •Note: other protocol defined Inclusion criteria may apply
排除标准
- •HLA-A*02:05 in either allele
- •Received or plans to receive the following therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy, Tyrosine kinase inhibitor (TKI) (e.g. pazopanib), Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors,), Anti-cancer Vaccine, Gene therapy using an integrating vector (subjects who have received a gene therapy using a lentiviral vector may be eligible for the study), Corticosteroids or any other immunosuppressive therapy, Investigational treatment or interventional clinical trial, Allogeneic hematopoietic stem cell transplant, Radiotherapy to the target lesions, Major surgery
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
- •History of autoimmune or immune mediated disease
- •Symptomatic CNS metastases including leptomeningeal disease.
- •Other prior malignancy that is not considered by the Investigator to be in complete remission
- •Clinically significant cardiovascular disease
- •Uncontrolled intercurrent illness
- •Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
- •Pregnant or breastfeeding
- •Note: other protocol defined Exclusion criteria may apply.
研究组 & 干预措施
Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells
Experimental
干预措施: afamitresgene autoleucel (previously ADP-A2M4) (Genetic)
结局指标
主要结局
Overall Response Rate (ORR) (Cohort 1)
时间窗: From T-cell infusion until disease progression/recurrence as of data cut off (up to 2 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
Percentage of participants with confirmed tumor response (complete \[CR\] or partial \[PR\] response) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Independent Radiologist review (Cohort 1)
次要结局
- Best Overall Response (BOR) (Cohort 1)(From T-cell infusion until disease progression/recurrence as of data cut off (up to 2.6 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.)
- Duration of Response (DoR) (Cohort 1)(From initial confirmed response (CR or PR) until PD (or censored date) as of data cut off.)
- Progression Free Survival (PFS) (Cohort 1)(From T-cell infusion until first documented PD or death due to any cause (or censored date), whichever occurs first, as of data cut off (up to 2.6 years). Response was assessed at Week 4, 8,12,16, 24, and every 2 months until confirmed PD)
- Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1)(AEs, SAEs, and AESIs were collected at each visit from the start of lymphodepletion of the first subject until the last subject discontinued the interventional phase in cohort 1 as of the safety cut off (up to 3.2 years).)
- The Number of Participants With Replication Competent Lentivirus (RCL)(From T-cell infusion to months 3, 6, and 12 post-infusion, then annually post-infusion (up to 2.8 years as of the data cut off).)
- Insertional Oncogenesis (IO)(From 10 months post T-cell infusion up to 20 months post T-cell infusion (as of the data cut off))
- Quantitation of Genetically Engineered T-cells in PBMCs(2.5 years)
- Time to Response (TTR) (Cohort 1)(From T-cell infusion until first documented confirmed CR or confirmed PR. Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.)
- Overall Survival (OS) (Cohort 1)(From T-cell infusion to death due to any reason (or censored date) as of data cut off (up to 2.6 years).)
- Peak Persistence (Cohort 1)(From T-cell infusion to 3.2 years (as of data cut off).)
- In Vitro Diagnostic (IVD) Assay for Screening(2.5 years)
- Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs(2.5 years)
研究者
研究点 (26)
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相关资讯
MAGEA4-Targeted Therapies Show Promise in Solid Tumors Beyond Synovial Sarcoma- Afamitresgene autoleucel (afami-cel; Tecelra) received FDA approval for unresectable or metastatic synovial sarcoma, marking the first engineered cell therapy approval for a solid tumor.
- MAGEA4, the target of afami-cel, is expressed in various solid tumors, including NSCLC, head and neck squamous cell carcinoma, and melanoma, making it a target for T-cell therapies.
- Early-phase studies of IMA401, a MAGEA4/8-directed bispecific T-cell engager, and MT-601, a multi-tumor-associated antigen-specific T-cell agent, show promising response rates in solid tumors and lymphoma, respectively.last yearFDA Approves Afami-Cel (Tecelra) for Advanced Synovial Sarcoma with MAGE-A4 Expression- The FDA granted accelerated approval to afami-cel (Tecelra) for unresectable or metastatic synovial sarcoma in adults after prior chemotherapy.
- Approval is based on the SPEARHEAD-1 trial, showing a 43% overall response rate and a 4.5% complete response rate in treated patients.
- Afami-cel is a personalized T-cell receptor therapy targeting the MAGE-A4 protein, requiring HLA-A\*02:01P, -A\*02:02P, -A\*02:03P, or -A\*02:06P positivity.
- This approval marks the first engineered cell therapy for a solid tumor cancer and provides a new treatment option for synovial sarcoma after a decade.2 years ago