A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Evaluate changes in the electrocardiogram QT interval that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab). [Safety]
研究概览
简要总结
This is an open-label Phase 1/2a study. Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a clinically available check point inhibitor (CPI).
During the monotherapy phase of Phase 1, one patient will be treated intradermally every 2 weeks for 6 weeks (4 doses) with an initial dose of the BC1 cell line. If this dose is tolerated, the next patient will receive an increased dose of BC1. If once again tolerated, the third patient will receive a further dose increase of the BC1. Once at least 3 patients have been safely treated with the BC1 cell line, with no dose-limiting toxicity (DLT), the combinational phase of the study will commence.
Following the monotherapy phase, patients will be treated with BC1 and the Bria-OTS regimen (see below) every 3 weeks, plus a CPI at the FDA approved labelled dose and schedule. There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risk(s).
During the Phase 1 combination and Phase 2 expansion phases, all patients will be treated with BC1 cells as part of the Bria-OTS regimen, which includes cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell inoculation, and peginterferon alpha-2a administered on the same day, following BC1 cell inoculation.
详细描述
Open-label Phase 1/2a study.
Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a check point inhibitor (CPI).
During the monotherapy phase of Phase 1, one patient will be treated intradermally every 2 weeks for 6 weeks (4 doses) with an initial dose of the BC1 cell line. If this dose is tolerated, the next patient will receive an increased dose of BC1 cells. If once again tolerated, the third patient will receive a further increased dose of BC1. Once at least 3 patients have been safely treated with the BC1 cell line, with no dose-limiting toxicity (DLT), the combinational phase of the study will commence.
Following the monotherapy phase, patients will be treated with BC1 and the Bria-OTS regimen (see below) every 3 weeks, plus a CPI at the FDA approved labelled dose and schedule. There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risk(s).
During the Phase 1 combination and Phase 2 expansion phases, all patients will be treated with BC1 cells as part of the Bria-OTS regimen, which includes cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell inoculation, and peginterferon alpha-2a administered on the same day, following BC1 cell inoculation.
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
- •Histological confirmed recurrent metastatic breast cancer which has failed prior
- •therapy defined as:
- •Human epidermal growth factor 2 (EGFR2, HER2) positive tumors must have failed therapy with at least 2 anti-HER2 agents
- •HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy and previously treated with at least 2 hormone based targeted therapy containing regimens.
- •Triple-negative and inflammatory tumors must have exhausted other curative intent therapies including prior treatment with a taxane and platinum-based agent
- •All other MBC types must have exhausted other curative intent therapies including any genomic or germline directed targeted therapy having available approved drug(s)
- •Patients with new or progressive breast cancer metastatic to the brain will be eligible, provided:
- •i. The brain metastases must be clinically stable (without evidence of progressive disease by imaging) for at least 4 weeks, prior to first dose.
- •ii. There is no need for steroids and patients have not had steroids for at least 2 weeks prior to the first dose.
- •Be 18 years of age or older.
- •Have expected survival of at least 4 months.
- •Have adequate performance status (up to and including ECOG 2)
- •Patients must be stable with all known or expected toxicities from previous treatment including:
- •Prior immune related toxicity must not have exceeded Grade 2 with exception of stable endocrinopathy (endocrinopathy if well-managed, is not exclusionary).
- •Toxicity of prior therapy that has not recovered to ≤ grade 1 or baseline (with the exception of any grade of alopecia, adequately treated endocrinopathy, and anemia not requiring transfusion support).
排除标准
- •Concurrent anti-cancer treatment.
- •Recent chemotherapy, radiotherapy, or other anti-cancer treatment within 3 weeks of first protocol treatment.
- •Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
- •History of clinical hypersensitivity to the designated therapy, as specified in the protocol or to any components used in the preparation of any cell line in this study.
- •History of clinical hypersensitivity to any protocol specified therapy.
- •BUN >30 in conjunction with a creatinine >2, or calculated creatinine clearance (CrCl) <30 mL/min (GFR can be used in place of creatinine or CrCl).
- •Absolute granulocyte count < 1000; platelets <50,
- •Bilirubin >2.0; alkaline phosphatase >4x upper limit of normal (ULN); ALT/AST >2x ULN. For patients with hepatic metastases, ALT/AST >5x ULN is exclusionary.
- •Proteinuria >1+ on urinalysis or >1 gm/24hr.
- •New York Heart Association stage 3 or 4 cardiac disease.
- •A pleural or pericardial effusion of moderate severity or worse.
- •Any woman of childbearing potential (i.e., has had a menstrual cycle within the past year and has not been surgically sterilized), unless she: agrees to take appropriate precautions to avoid becoming pregnant during the study and has a negative serum pregnancy test within 7 days prior to starting treatment.
- •Men who are fertile/reproductively competent, should take appropriate precautions to avoid fathering a child for the duration of the study.
- •Women who are pregnant or nursing.
- •Patients with concurrent second malignancy.
- •Persons with previous malignancies requiring treatment within the past 24 months.
- •Patients who have clinical or laboratory features indicative of AIDS and are HIV positive (by self-report).
- •Have a diagnosis of immunodeficiency, or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent), or any other form of immunosuppressive therapy within 21 days prior to first dose of study treatment.
- •Patients who are on treatment for an autoimmune disease, unless specifically approved by the Investigator and the Sponsor.
- •Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator and Sponsor.
- •Patients may not be on a concurrent clinical trial, unless approved by Investigator and Sponsor.
结局指标
主要结局
Evaluate changes in the electrocardiogram QT interval that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab). [Safety]
时间窗: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o Electrocardiograms (ECG) with measurement of the QT interval
Evaluate the proportion of patients with abnormal physical examination findings including vital signs
时间窗: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Physical Examination Findings and Abnormal Vital Signs
Safety as assessed by adverse events (AEs), including serious adverse events (SAEs)
时间窗: Throughout study period plus 4 weeks, approximately 16 weeks total
Total number of AEs
Evaluate the Proportion of Patients with Abnormalities in Safety Laboratory Parameters that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab)
时间窗: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters
次要结局
- Tumor response as assessed by Non-progressive rate (aka: clinical benefit rate), defined as CR, PR, or stable disease (SD) per RECIST 1.1 and as determined by local standard of care imaging and investigators(Throughout study period plus 4 weeks, approximately 16 weeks total)
- Tumor response as assessed by Clinical response rate as determined by local standard of care imaging and investigators(Throughout study period plus 4 weeks, approximately 16 weeks total)
- Tumor response as assessed by Duration of response (DoR)(Throughout study period plus 4 weeks, approximately 16 weeks total)
- Tumor response as assessed by Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Throughout study period plus 4 weeks, approximately 16 weeks total)