A Phase 1 Study to Assess the Safety and Efficacy of LYL845 in Adults With Relapsed and/or Refractory Metastatic or Locally Advanced Melanoma and Selected Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 39
- 试验地点
- 18
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).
详细描述
This is an open-label, multi-center, dose-escalation study with expansion cohorts, designed to evaluate the safety and anti-tumor activity of LYL845, an epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy, in participants with relapsed or refractory (R/R) metastatic or locally advanced melanoma, non-small cell lung cancer (NSCLC), and colorectal cancer (CRC). During the dose-escalation phase of the study (Part A), participants with melanoma will be enrolled. Once a safe recommended Phase 2 dose range (RP2DR) has been established in Part A, enrollment will be expanded (Part B) to include additional participants with melanoma, NSCLC and CRC.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years up to ≤ 75 years at the time of informed consent
- •Confirmed diagnosis of melanoma, non-small cell lung cancer (NSCLC), or colorectal cancer (CRC) that is metastatic or locally advanced or unresectable and is relapsed and/or refractory (R/R) after standard therapy for each tumor histology
- •Participants must have received prior systemic treatment for their metastatic disease or locally advanced disease based on tumor type as follows:
- •Melanoma: participants with disease progression following an immune checkpoint inhibitor (CPI)
- •NSCLC: participants with disease progression following at least 1 approved systemic therapy, including an immune CPI-containing regimen for appropriate patients or an approved targeted therapy for known molecular abnormalities if applicable to their disease
- •CRC: participants with disease progression following at least 1 line of therapy, including a fluoropyrimidine with oxaliplatin or irinotecan. Microsatellite instability (MSI) high/mismatch repair deficient (dMMR) CRC participants must have disease progression following systemic therapy with immune CPIs.
- •Measurable disease including at least 1 lesion that is safely resectable AND a target lesion to measure response and an additional lesion for biopsy
- •Eastern Cooperative Oncology Group (ECOG) performance status of 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
- •Fully recovered from toxicity from prior systemic anticancer therapy
排除标准
- •Prior treatment with adoptive cellular therapy
- •Prior solid organ transplantation
- •Central nervous system (CNS) involvement of disease that is extensive, symptomatic or untreated, or patients with leptomeningeal disease
- •Uncontrolled or symptomatic pleural effusion or ascites
- •Untreated or active systemic infection
- •Active autoimmune disease requiring treatment or primary immunodeficiency syndrome
- •Systemic corticosteroids at a dose of >10 mg of prednisone or equivalent per day
- •Other primary malignancy within 3 years prior to enrollment
- •Impaired cardiac function or clinically significant cardiovascular disease
- •Required chronic anticoagulation, such as warfarin, low molecular weight heparin, or Factor Xa inhibitors
- •Pregnant or nursing (lactating) women
研究组 & 干预措施
Experimental LYL845
Epigenetically reprogrammed tumor infiltrating lymphocyte (TIL) therapy
干预措施: LYL845 (Biological)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: Up to 28 days
Evaluate incidence of dose-limiting toxicities (DLTs)
Determine recommended Phase 2 Dose Range (RP2DR)
时间窗: Up to 2 years
Determine the recommended Phase 2 dose range (during dose-escalation phase)
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Evaluate incidence of treatment-emergent adverse events (TEAEs)
Severity of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Evaluate severity of treatment-emergent adverse events (TEAEs)
次要结局
- Overall response rate (ORR) by RECIST, version 1.1(up to 2 years)
- Overall survival (OS)(up to 2 years)
- Duration of response (DOR)(up to 2 years)
- Progression-free survival (PFS)(up to 2 years)