A Phase 1, Open-Label Study of FT836, an Off-the-Shelf CAR T-Cell Therapy, With or Without Chemotherapy and/or Monoclonal Antibodies, in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 119
- 试验地点
- 8
- 主要终点
- Number of participants with dose limiting toxicities (DLTs)
研究概览
简要总结
This is a Phase 1 study of FT836 administered in participants with advanced solid tumors. The primary objectives of the study are to evaluate the safety and tolerability of FT836 with or without chemotherapy and/or trastuzumab or cetuximab, and to determine the recommended phase 2 dose (RP2D) of FT836 with or without chemotherapy and/or trastuzumab or cetuximab
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •For all regimens, disease that is not amenable to curative therapy and that has relapsed or progressed following at least one line of prior systemic therapy.
- •Evidence of adequate organ function as determined by all of the following:
- •Absolute neutrophil count (ANC) >1000/µL without growth factor support within 7 days prior to start of first study intervention
- •Platelet count ≥75,000/µL without transfusion support within 14 days prior to start of first study intervention
- •Estimated creatinine clearance ≥50 mL/minute by Cockcroft-Gault method or other standard institutional method
- •Total bilirubin ≤1.5 × upper limit of normal (ULN); for participants with documented Gilbert syndrome, total bilirubin must be ≤3 ×ULN
- •Aspartate transaminase (AST) ≤3 × ULN or alanine transaminase (ALT) ≤3 × ULN; in participants with documented liver metastases, AST or ALT ≤5 × ULN
- •Alkaline phosphatase (ALP) ≤2.5 × ULN; in participants with documented liver or bone metastases, ALP ≤5 × ULN
- •Oxygen saturation >90% on room air
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or
- •Presence of measurable disease by RECIST, v1.1 assessed within 28 days prior to start of first study intervention.
- •Presence of baseline safely accessible lesions of adequate size for on-treatment biopsies (exceptions for lesion size may be granted with medical monitor approval) and participant willingness to undergo protocol prescribed on-treatment biopsies.
排除标准
- •Clinically significant cardiovascular disease including any of the following: uncontrolled/ unstable cardiac arrhythmias, myocardial infarction within 6 months prior to start of first study intervention, unstable angina or congestive heart failure of New York Heart Association (NYHA) Grade 2 or higher, or cardiac ejection fraction <50%.
- •Receipt of any biological therapy, chemotherapy, investigational therapy, or radiation therapy within 2 weeks or five half-lives prior to start of first study intervention, whichever is shorter.
- •Known active central nervous system (CNS) involvement by malignancy. Participants with prior CNS involvement from their malignancy must have completed effective treatment of their CNS disease with no symptoms of disease in the absence of steroid treatment and at least stable findings on relevant CNS imaging and no evidence of leptomeningeal disease for at least 4 weeks prior to study enrollment.
- •Non-malignant CNS disease such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease or receipt of medications for these conditions within 6 months prior to study enrollment.
- •Currently receiving or likely to require systemic immunosuppressive therapy (e.g., prednisone ≥5 mg daily) for any reason from start of first study intervention to Day 29 with the exception of corticosteroids as a premedication for chemotherapy side effects per institutional standard of care or as mandated by the protocol.
- •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.
- •Grade ≥2 peripheral neuropathy limiting instrumental activities of daily living.
研究组 & 干预措施
Regimen D1
SOC chemotherapy followed by FT836 combined with cetuximab
干预措施: Cetuximab (Drug)
Regimen D
CY/FLU followed by FT836 combined with cetuximab
干预措施: FT836 (Drug)
Regimen F1
SOC chemotherapy followed by FT836 combined with trastuzumab
干预措施: Trastuzumab (Drug)
Regimen B
Standard-of-care (SOC) chemotherapy followed by FT836
干预措施: FT836 (Drug)
Regimen E
FT836 combined with trastuzumab
干预措施: Trastuzumab (Drug)
Regimen A
CY/FLU followed by FT836
干预措施: FT836 (Drug)
Regimen E
FT836 combined with trastuzumab
干预措施: FT836 (Drug)
Regimen C
FT836 combined with cetuximab
干预措施: Cetuximab (Drug)
Regimen F
CY/FLU followed by FT836 combined with trastuzumab
干预措施: FT836 (Drug)
Regimen C
FT836 combined with cetuximab
干预措施: FT836 (Drug)
Regimen F
CY/FLU followed by FT836 combined with trastuzumab
干预措施: Trastuzumab (Drug)
Regimen D
CY/FLU followed by FT836 combined with cetuximab
干预措施: Cetuximab (Drug)
Regimen F1
SOC chemotherapy followed by FT836 combined with trastuzumab
干预措施: FT836 (Drug)
Regimen D1
SOC chemotherapy followed by FT836 combined with cetuximab
干预措施: FT836 (Drug)
结局指标
主要结局
Number of participants with dose limiting toxicities (DLTs)
时间窗: From Day 1 through Day 29 of Cycle 1( each cycle is 56 days)
The number of participants experiencing ≥1 DLT will be reported.
Severity of DLTs
时间窗: From Day 1 through Day 29 of Cycle 1( each cycle is 56 days)
The severity of DLTs will be determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, v5.0).
次要结局
- Overall Response Rate (ORR)(Up to approximately 24 months)
- Duration of Response (DOR)(Up to approximately 24 months)
- Overall Survival (OS)(Up to approximately 24 months)
- Progression-Free Survival (PFS)(Up to approximately 24 months)