A Phase 1b Study of TBio-4101 (Autologous Selected and Expanded Tumor-Infiltrating Lymphocytes [TIL]) and Pembrolizumab in Patients With Advanced Solid Tumor Malignancies (STARLING)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 31
- 试验地点
- 13
- 主要终点
- Safety and tolerability
研究概览
简要总结
A multicenter trial to investigate TBio-4101, an autologous, neoantigen-selected, tumor-reactive TIL product, in patients with advanced solid malignancies.
详细描述
This is a Phase 1 study to investigate TBio-4101. TBio-4101 is an autologous tumor infiltrating lymphocyte (TIL) therapy that utilizes tumor specific antigens to select, sort, and expand patient-specific tumor-reactive T-cells to be reinfused into the patient. The adoptive cell therapy is further enhanced through the use of non-myeloablative chemotherapy prior to TIL infusion, followed by the TIL plus IL-2 infusion. Low-dose radiation therapy is administered prior to and after TIL plus IL-2 infusion. Pembrolizumab is provided after the resolution of IL-2 toxicities. The trial is open to solid tumors of varying tumor mutational burdens.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Advanced or metastatic breast carcinoma, colorectal adenocarcinoma, uveal melanoma, cutaneous melanoma, non-small cell lung cancer, or head and neck squamous cell carcinoma that has failed or is refractory to standard of care therapy
- •Have at least one target lesion that can be used for response assessments and have at least 1 tumor amenable for tissue harvest for TIL manufacturing.
- •ECOG performance status of 0 or 1
- •Demonstrate adequate organ function
- •Additional inclusion criteria exist
排除标准
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years
- •Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive
- •Currently infected with HIV Type 1 and Type 2, hepatitis B virus (HBV), hepatitis C virus (HCV), treponema pallidum (e.g., syphilis), West Nile virus (WNV), Human T-lymphotropic virus types 1 or II (HTLV I/II), or cytomegalovirus (CMV)
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable
- •Serious cardiac condition, such as uncontrolled hypertension, concurrent congestive heart failure, prior history of Class III/IV cardiac disease (New York Heart Association [NYHA]), history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment. Patients who are > 60 years of age must undergo cardiology clearance exam and cardiac stress test.
- •Prior cell therapy or organ transplant
- •History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, IL-2, or pembrolizumab, or any of their constituents
- •LVEF ≤ 45%
- •FEV1 ≤ 60% of predicted value and DLCO (corrected) < 60% of predicted value
- •Chronic anti-coagulant therapy that cannot either be discontinued or temporarily changed
- •Additional exclusion criteria exist
研究组 & 干预措施
Breast Cancer
Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.
干预措施: TBio-4101 (Biological)
Breast Cancer
Patients with locally advanced or metastatic breast cancer that has failed or is intolerant to standard of care therapies. Includes, HER2+, HER 2-, TNBC.
干预措施: Pembrolizumab (Drug)
Colorectal carcinoma
Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.
干预措施: TBio-4101 (Biological)
Colorectal carcinoma
Patients with advanced, metastatic colorectal adenocarcinoma who have failed or are intolerant to at least one line of therapy that included either irinotecan or oxaliplatin.
干预措施: Pembrolizumab (Drug)
Uveal Melanoma
Patients with advanced, metastatic uveal melanoma.
干预措施: TBio-4101 (Biological)
Uveal Melanoma
Patients with advanced, metastatic uveal melanoma.
干预措施: Pembrolizumab (Drug)
Cutaneous Melanoma
Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.
干预措施: TBio-4101 (Biological)
Cutaneous Melanoma
Patients with cutaneous melanoma who have experienced disease progression following a PD-1 or PD-L1 inhibitor.
干预措施: Pembrolizumab (Drug)
Non-Small Cell Lung Cancer
Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.
干预措施: TBio-4101 (Biological)
Non-Small Cell Lung Cancer
Patients with non-small cell lung cancer who have experienced disease progression following platinum containing chemotherapy and/or PD-1 or PD-L1 inhibitor.
干预措施: Pembrolizumab (Drug)
Head and Neck Squamous Cell Carcinoma
- Patients with head and neck squamous cell carcinoma who have received no prior therapy for metastatic disease
- Patients with head and neck squamous cell carcinoma who are PD-1/PD-L1 inhibitor naïve at the time of TIL harvest and will be treated with TBio-4101 at the time of progression, inadequate response or intolerance to the PD-1/PD-L1 inhibitor-based standard of care regimen given on study.
干预措施: TBio-4101 (Biological)
Head and Neck Squamous Cell Carcinoma
- Patients with head and neck squamous cell carcinoma who have received no prior therapy for metastatic disease
- Patients with head and neck squamous cell carcinoma who are PD-1/PD-L1 inhibitor naïve at the time of TIL harvest and will be treated with TBio-4101 at the time of progression, inadequate response or intolerance to the PD-1/PD-L1 inhibitor-based standard of care regimen given on study.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Safety and tolerability
时间窗: 25 months
The incidence of treatment-emergent adverse events will be tabulated using NCI CTCAE v5.0
次要结局
- Proportion of patients with a response (ORR)(25 months)
- Estimated Disease Control Rate (DCR)(25 months)
- Estimated Duration of Response (DoR)(25 months)