Phase I Clinical Trial of Autologous Folate Receptor-Alpha Redirected T Cells in Patients With FRa+ Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Incidence of adverse events as assessed by CTCAE V5.0
研究概览
简要总结
This is a Phase I open-label clinical trial to assess the safety, feasibility, and preliminary efficacy of intrapleural administration of MOv19-BBz CAR T cells in patients with FRa+ cancers. This study will be initiated in patients with metastatic or recurrent non-small cell lung cancer (NSCLC) only. Subjects will receive a single dose of MOv19-BBz CAR T cells via intrapleural infusion following lymphodepleting chemotherapy. Subjects without an existing intra-pleural catheter will have a temporary pleural catheter placed for the study. Subjects may initiate treatment with commercial checkpoint inhibitors per routine care beginning at least 28 days after receiving MOv19-BBz CAR T cells.
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
- •Signed informed consent form
- •Documentation of tumor FRa expression by IHC at the Hospital of the University of Pennsylvania (≥ 10% of tumor cells). Subjects must have archived tumor tissue available.
- •Disease-specific criteria:
- •a. NSCLC Patients: i. Metastatic or recurrent lung adenocarcinoma with cytologically or pathologically confirmed malignant pleural effusion.
- •ii. Failure of at least one prior line of standard of care therapy for advanced stage disease.
- •Patients must have evidence of active disease as defined by RECIST 1.1 criteria
- •Patients with asymptomatic CNS metastases that have been treated (and are off steroids for the treatment of CNS disease) are allowed. They must meet the following criteria
- •No concurrent treatment for the CNS disease
- •No progression of CNS metastasis on MRI at screening
- •No evidence of leptomeningeal disease or cord compression
- •Adequate organ function defined as:
- •Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 30 cc/min; Patient must not be on dialysis
- •ALT/AST ≤ 3x upper limit of normal range
- •Serum total bilirubin ≤ 1.5 mg/dl, unless the subject has Gilbert's syndrome (if so, serum total bilirubin must be ≤ 3.0 mg/dl)
- •Must have a minimum level of pulmonary reserve defined as < Grade 1 dyspnea and pulse oxygen > 92% on room air
- •Left Ventricle Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO or MUGA
- •Male or female age ≥ 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status that is either 0 or 1
- •Subjects must be a possible clinical candidate for standard of care treatment with a commercial checkpoint inhibitor, as per physician-investigator assessment.
排除标准
- •Any clinically significant pleural effusion that cannot be drained with standard approaches.
- •Patients with significant lung disease as follows:
- •Patients with radiographic evidence of greater than lobar lymphangitic pulmonary involvement, greater than lobar bronchial wall thickening suggestive of peribronchial lymphatic disease extension, and/or evidence of extensive bilateral parenchymal metastatic burden.Note: "Greater than lobar" = "in more than 1 lobe".
- •Patients with radiographic and/or clinical evidence of active radiation pneumonitis.
- •Patients with radiographic evidence of underlying interstitial lung disease, including evidence of unresolved drug toxicity from any agent (e.g. chemotherapy, targeted agents, amiodarone, nitrofurantoin, etc.).
- •Patients with radiographic evidence of significant pleural effusion that is not readily amenable to minimally invasive drainage.
- •Active hepatitis B or hepatitis C infection
- •Any other active, uncontrolled infection
- •Class III/IV cardiovascular disability according to the New York Heart Association Classification
- •Active invasive cancer, other than the proposed cancer included in this protocol, within 2 years prior to eligibility confirmation by a physician-investigator. [Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer) may still be eligible].
- •Dependence on systemic steroids or immunosuppressant medications.
- •Pregnant or nursing (lactating) patients. Participants of reproductive potential must agree to use acceptable birth control methods
- •Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥ 10mg of prednisone daily. Patients with autoimmune neurologic diseases (such as MS) will be excluded.
- •History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
研究组 & 干预措施
Dose Level 1 (DL1)
single dose of 5x10(7) MOv19-BBz CAR T cells administered via intrapleural infusion following lymphodepleting chemotherapy
干预措施: MOv19-BBz CAR T cells (Biological)
Dose Level 1 (DL1)
single dose of 5x10(7) MOv19-BBz CAR T cells administered via intrapleural infusion following lymphodepleting chemotherapy
干预措施: Cyclophosphamide/Fludarabine (Drug)
Dose Level 1 (DL1)
single dose of 5x10(7) MOv19-BBz CAR T cells administered via intrapleural infusion following lymphodepleting chemotherapy
干预措施: FRa Expression Testing (Device)
Dose Level -1 (DL-1)
2.5x10(7) MOv19-BBz CAR T cells adminstered via intrapleural infusion, following lymphodepleting chemotherapy. This dose level will only be explored if ≥ 2 TLTs occur at any time in DL1.
干预措施: MOv19-BBz CAR T cells (Biological)
Dose Level -1 (DL-1)
2.5x10(7) MOv19-BBz CAR T cells adminstered via intrapleural infusion, following lymphodepleting chemotherapy. This dose level will only be explored if ≥ 2 TLTs occur at any time in DL1.
干预措施: Cyclophosphamide/Fludarabine (Drug)
Dose Level -1 (DL-1)
2.5x10(7) MOv19-BBz CAR T cells adminstered via intrapleural infusion, following lymphodepleting chemotherapy. This dose level will only be explored if ≥ 2 TLTs occur at any time in DL1.
干预措施: FRa Expression Testing (Device)
结局指标
主要结局
Incidence of adverse events as assessed by CTCAE V5.0
时间窗: Up to 15 years post-MOv19-BBz CAR T cell administration
Type, frequency, severity, and attribution of adverse events.
Occurrence of treatment-limiting toxicities (TLTs)
时间窗: 28 days post-MOv19-BBz CAR T cell administration
Unacceptable toxicity as defined by the protocol.
次要结局
- Evaluate study feasibility(6 months)
- Objective Response Rate (ORR)(Up to 12 months following treatment with MOv19-BBz CAR T cells)
- Duration of Response (DOR)(Up to 15 years following treatment with MOv19-BBz CAR T cells)
- Progression Free Survival (PFS)(Up to 15 years following treatment with MOv19-BBz CAR T cells)
- Overall Survival (OS)(Up to 15 years following treatment with MOv19-BBz CAR T cell)