A Phase 1 Study of FT825/ONO-8250, an Off-the-Shelf CAR T-Cell Therapy, With or Without Monoclonal Antibodies, in HER2-Positive or Other Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 351
- 试验地点
- 14
- 主要终点
- Severity of AEs
研究概览
简要总结
This is a phase 1 study designed to evaluate the safety, tolerability, and antitumor activity of FT825 (also known as ONO-8250) with or without monoclonal antibody therapy following chemotherapy in participants with advanced human epidermal growth factor receptor 2 (HER2)-positive or other advanced solid tumors. The study will consist of a dose-escalation stage, followed by an expansion stage to further evaluate the safety and activity of FT825 in indication-specific cohorts.
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
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
- •Histopathological or cytologically confirmed locally advanced or metastatic cancer that meets protocol-defined criteria
- •Disease that is not amenable to curative therapy, with prior therapies defined by specific tumor types
- •Contraceptive use by women and men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
- •Presence of measurable disease by RECIST, v1.1 assessed within 28 days prior to start of first study intervention
- •Anticipated life expectancy of at least 3 months
排除标准
- •Females who are pregnant or breastfeeding
- •Evidence of inadequate organ function
- •Clinically significant cardiovascular disease
- •Known active central nervous system (CNS) involvement by malignancy
- •Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions within 2 years prior to study enrollment
- •Active bacterial, fungal, or viral infections
- •Prior receipt of chimeric antigen receptor (CAR) T-cell therapy, other cellular therapy, or a FATE investigational human induced pluripotent stem cell (iPSC) product
- •History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out based on imaging at screening
- •Any history of Grade ≥3 immune-related AE or Grade ≥2 eye toxicity attributed to prior cancer immunotherapy, other than endocrinopathy managed with replacement therapy or asymptomatic elevation of serum amylase or lipase
- •Active or history of autoimmune disease or immune deficiency
- •Receipt of an allograft organ transplant
研究组 & 干预措施
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: FT825 (Drug)
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Fludarabine (Drug)
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Cyclophosphamide (Drug)
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Bendamustine (Drug)
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Docetaxel (Drug)
Regimen A: FT825
Participants with advanced HER2-expressing solid tumors receive FT825 following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Cisplatin (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: FT825 (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Fludarabine (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Cyclophosphamide (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Bendamustine (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Docetaxel (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Cisplatin (Drug)
Regimen B: FT825 + Cetuximab
Participants with advanced epidermal growth factor receptor (EGFR)-expressing solid tumors receive FT825 in combination with cetuximab following chemotherapy in Cycle 1 (each cycle is approximately 61 days). Based on the safety, tolerability, and radiographically confirmed clinical benefit to treatment in Cycle 1, participants may be considered for an additional treatment cycle (Cycle 2 retreatment).
干预措施: Cetuximab (Drug)
结局指标
主要结局
Severity of AEs
时间窗: Up to approximately 2 years
Severity of AEs will be determined according to appropriate rating scales for the type of event reported.
Number of participants with dose limiting toxicities (DLTs)
时间窗: Up to approximately 29 days
The number of participants with DLTs will be reported.
Number of participants with treatment-emergent adverse events (TEAEs)
时间窗: Up to approximately 2 years
The number of participants with TEAEs will be reported.
次要结局
- Investigator-Assessed Duration of Response (DOR)(Up to approximately 2 years)
- Investigator-Assessed Overall Response Rate (ORR)(Up to approximately 2 years)
- Progression-Free Survival (PFS)(Up to approximately 2 years)
- Plasma Concentration of FT825(At designated time points up to approximately 56 days)
- Overall Survival (OS)(Up to approximately 2 years)