A Phase 1 Study to Assess the Safety and Efficacy of LYL797, ROR1-Targeting CAR T Cells, in Adults With Relapsed and/or Refractory Solid-Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 16
- 主要终点
- Evaluate incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
This study will evaluate the safety and tolerability of LYL797, a ROR1-targeted CAR T-cell therapy, in patients with ROR1+ relapsed or refractory triple negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). The first part of the study will determine the safe dose for the next part of the study, and will enroll TNBC and NSCLC patients. The second part of the study will test that dose in additional TNBC and NSCLC patients.
详细描述
This Phase 1, single-arm, open-label, multi-center, dose-escalation and -expansion study will evaluate the safety and tolerability of LYL797, ROR1-targeting CAR T cells, in adults with relapsed and/or refractory ROR1+ triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). The dose-escalation phase includes TNBC and NSCLC patients, and will investigate 4 dose levels to determine the recommended Phase 2 dose (RP2D). The dose-expansion phase will enroll both TNBC and NSCLC patients at the RP2D.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •≥ 18 years of age at time of informed consent
- •Histologically confirmed TNBC or NSCLC that is relapsed or refractory, metastatic or locally advanced and unresectable that is ROR1+ by central laboratory immunohistochemistry (IHC)
- •Measurable disease including a target lesion and an additional lesion for biopsy
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate organ and marrow function
- •Women of childbearing potential must have a negative pregnancy test at screening
- •All participants must agree to practice highly effective methods of contraception
排除标准
- •Prior treatment with any adoptive T-cell therapy or anti-ROR1 therapy
- •Prior solid organ transplantation
- •Active, untreated brain metastasis or leptomeningeal disease; stable, treated brain involvement by disease is allowed
- •Untreated or active infection at the time of screening or leukapheresis
- •HIV-positive, HTLV-1-positive, active acute or chronic HBV or HCV, or active tuberculosis
- •Impaired cardiac function or clinically significant cardiac disease
- •Uncontrolled pleural or pericardial effusion
- •Systemic corticosteroids or other immunosuppressive medications within 14 days of leukapheresis
- •Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors
- •Pregnant or lactating/nursing women
研究组 & 干预措施
Experimental LYL797
ROR1-targeted CAR T cells
干预措施: LYL797 (Biological)
结局指标
主要结局
Evaluate incidence of dose-limiting toxicities (DLTs)
时间窗: Up to 28 days
Incidence of dose-limiting toxicities (DLTs)
Evaluate incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Incidence of treatment-emergent adverse events (TEAEs)
Evaluate severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Severity of treatment-emergent adverse events (TEAEs)
Determine recommended Phase 2 Dose (RP2D)
时间窗: Up to 2 years
Dose-escalation phase to determine the recommended Phase 2 dose
次要结局
- Evaluate anti-tumor activity of LYL797 based on overall response rate (ORR) by RECIST, version 1.1(Up to 2 years)
- Evaluate duration of response (DOR)(Up to 2 years)
- Evaluate progression-free survival (PFS)(Up to 2 years)
- Evaluate overall survival (OS)(Up to 2 years)
- Evaluate maximum concentration of LYL797 (Cmax) of LYL797 in peripheral blood (PB) samples(Up to 2 years)
- Evaluate time to Cmax (Tmax) of LYL797 in peripheral blood (PB) samples(Up to 2 years)
- Evaluate area under the concentration-time curve (AUC) of LYL797 in the peripheral blood (PB)(Up to 2 years)
- Evaluate Persistence of LYL797 CAR T cells in peripheral blood samples(Up to 2 years)