A Phase 1, Open-Label, Dose-Escalation Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Combination of CLBR001, an Engineered Autologous T Cell Product, and ABBV-461, an Antibody-Based Biologic, in Subjects With Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 8
- 主要终点
- Number of subjects with adverse events as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS
研究概览
简要总结
The goal of this clinical trial is to evaluate CLBR001 and ABBV-461 as a treatment for patients with locally advanced or metastatic breast cancer. The goals are to establish the safety and efficacy of the combination therapy while establishing the optimal biologic doses.
Patients will be administered a single infusion of CLBR001 cells followed by cycles of ABBV-461 with regular assessments of safety and disease response to treatment.
详细描述
CLBR001 + ABBV-461 is novel switchable CAR-T cell combination therapy comprised of an autologous CAR-T product (CLBR001, the switchable CAR-T cell [sCAR-T]) and ABBV-461 (the "switch" biologic molecule). ABBV-461 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Refractory or relapsed locally advanced or metastatic breast cancer
- •Exhaused all standard of care therapy options
- •Measurable disease at time of screening in accordance with RECIST v1.1 criteria
- •Women or men age ≥18 years of age at time of consent
- •ECOG performance status 0 or 1
- •Must provide a biopsy sample obtained during the screening period, following the end of the most recent prior line of therapy
- •Adequate hematological, renal, and liver function
排除标准
- •History of a clinically significant infection within 4 weeks prior to consent
- •Active bacterial, viral, and/or fungal infection
- •Prior allogeneic stem cell transplant
- •Prior lentiviral- or retroviral-based therapy including CAR-T cell therapy
- •Prior lymphodepleting or T-cell cytotoxic therapy within 3 months of enrollment
- •Subjects receiving attenuated vaccines within 4 weeks of consent or need for live vaccine within 12 months of starting study therapy
- •History of significant cardiovascular conditions within the past 6 months
- •Subjects with a prior history of or concurrent malignancy whose natural history or treatment has the potential to interfere with either the safety or efficacy assessment of the investigational regimen
研究组 & 干预措施
Dose Escalation
Combination product CLBR001 + ABBV461 is administered in ascending dose level cohorts to determine the Optimal Biologic Dose (OBD) of CLBR001 + ABBV-461.
干预措施: Two Component Product CLBR001 + ABBV-461 (Biological)
结局指标
主要结局
Number of subjects with adverse events as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS
时间窗: To 1-year post administration of CLBR001
To assess the safety and tolerability in subjects by evaluating the frequency, relatedness, severity and duration of adverse events, as assessed by CTCAE v5.0 and ASTCT consensus grading criteria for CRS and ICANS.
Number of subjects with replication competent lentivirus
时间窗: To 1-year post administration of CLBR001
To assess the safety and tolerability in subjects by evaluating the number of subjects testing positive for replication competent lentivirus.
Number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS
时间窗: To 28-days post-first dose of ABBV-461
The number of dose-limiting toxicities as assessed by CTCAE v5.0 and ASTCT consensus grading for CRS and ICANS will be used to identify an Optimal Biologic Dose (OBD) of CLBR001 and ABBV-461.
次要结局
- Pharmacodynamics(To 1-year post administration of CLBR001)
- Assess Immunogenicity using Antidrug Antibodies(To 1-year post administration of CLBR001)
- Overall Best Objective Response(To 1-year post administration of CLBR001)
- Disease Control Rate(To 1-year post administration of CLBR001)
- Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Cmax(To 1-year post administration of CLBR001)
- Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : Tmax(To 1-year post administration of CLBR001)
- Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : AUC(To 1-year post administration of CLBR001)
- Evaluate Pharmacokinetics of CLBR001 + ABBV-461 : t(1/2)(To 1-year post administration of CLBR001)