A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of LYL273 in Patients With Relapsed or Refractory Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 155
- 试验地点
- 10
- 主要终点
- Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study
研究概览
简要总结
This is a Phase 1/2 open-label, multicenter study evaluating the safety and efficacy of LYL273 in participants with relapsed or refractory metastatic colorectal cancer.
详细描述
LYL273-101 (CARABiNER) is a Phase 1/2 open label, multicenter study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of LYL273, a GCC-targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release, in participants with relapsed or refractory metastatic colorectal cancer (mCRC).
The study may enroll multiple dose expansion cohorts at the Sponsor's discretion to further characterize the safety, feasibility, and preliminary antitumor activity of LYL273 under defined treatment conditions including those defined below.
- Cohorts to explore alternative mCRC patient populations
Expansion cohorts may enroll a broader array of the mCRC population as listed below:
- Earlier mCRC: Patients who have had a maximum of 1 prior line of systemic therapy
- Cohorts to explore LYL273 in combination with other anti-cancer therapies Expansion cohorts may explore LYL273 in combination with consolidative radiotherapy.
Up to 18 participants will be enrolled into each expansion cohort with up to approximately 95 patients enrolled in the Phase 1 portion of the study.
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
- •Adults > 18 years old
- •Clinical and histopathological diagnosis of relapsed or refractory metastatic colorectal cancer
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Limited liver disease (less than 7 lesions with largest lesion less than 3 cm)
- •No surgical options with curative intent
- •Received prior therapy with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy in the advanced or metastatic setting, an anti-vascular endothelial growth factor (anti-VEGF) biological therapy if not contraindicated, and if RAS wild-type an anti-epidermal growth factor receptor (anti-EGFR) therapy in a manner consistent with National Comprehensive Cancer Network (NCCN) guidelines. Treatment must have been discontinued for disease progression or intolerance to therapy
- •Have at least one extracranial measurable target lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 standard
排除标准
- •Participants with tumor lesion(s) in a location that may cause perforation of an organ or structure (such as the digestive tract, urinary bladder, or blood vessel) with LYL273 therapy
- •Active central nervous system (CNS) involvement by malignancy on magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT)
- •History of or active viral infection including human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •History or presence of CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS involvement in the 2-year period leading up to the study enrollment
- •No active infectious diseases or comorbid conditions that would interfere with safety or data quality
- •Pregnant or breast-feeding women
- •Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
LYL273
Single infusion of LYL273 at the dose assigned to an individual participant.
All participants will receive the same investigational therapy with the dose administered dependent upon the dose level they are assigned to in a sequential manner.
干预措施: LYL273 (Drug)
结局指标
主要结局
Incidence of adverse events (AEs) defined as dose-limiting toxicities (DLTs) during 3+3 dose escalation study
时间窗: Infusion (Day 0) up to Day 28
Maximum tolerable dose (MTD) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
时间窗: Infusion (Day 0) up to Day 28
Recommended Phase 2 dose (RP2D) based on incidence of dose-limiting toxicities (DLTs) during 3+3 dose escalation study
时间窗: Infusion (Day 0) up to Day 28
次要结局
- Tmax: The time to reach maximum(peak) in peripheral blood or other body fluid drug concentration after single dose administration (days)(Infusion (Day 0) up to 12 months post treatment)
- AUCTmax - 28d and/or AUCTmax - 84d: The area under curve (AUC) from time Tmax to day 28 and/or AUCTmax - 84d or other disease assessment days, in peripheral blood (days x copies/μg)(Infusion (Day 0) up to 12 months post treatment)
- AUC0 - 28d and/or AUC0 - 84d: The area under curve (AUC) from time zero to day 28 and/or day 84 in peripheral blood (days x copies/μg)(Infusion (Day 0) up to 12 months post treatment)
- Best overall response as measured by overall response rate based on the tumor size per Response Evaluation Criteria in Solid Tumors RECIST Version 1.1(Infusion (Day 0) up to approximately 12 months or until disease progression/recurrence)
- Duration of Response (DOR)(Infusion (Day 0) up to approximately 12 months)
- Progression Free Survival (PFS)(Day 30 (date of leukapheresis) up to approximately 13 months or until the earliest date of disease progression per RECIST 1.1, or death from any cause, whichever comes first.)
- Overall Survival (OS)(Day 30 (date of leukapheresis) up to approximately 13 months or until death from any cause)
- Copy number of Guanylate Cyclase C (GCC) by Quantitative Polymerase Chain Reaction (qPCR)(Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months))
- Copy number of each individual CD19 by Quantitative Polymerase Chain Reaction (qPCR)(Infusion, Inpatient Monitoring and Post Treatment Period (Up to 12 months))
- Cytokine level in serum(Infusion (Day 0) up to 12 months post treatment)
- AUC0 - Tmax: The area under curve (AUC) from time zero to Tmax in peripheral blood (days x copies/μg)(Infusion (Day 0) up to 12 months post treatment)
- Cmax: The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (copies/μg)(Infusion (Day 0) up to 12 months post treatment)