An Open Label, Phase 1 Trial of LVGN6051 as Single Agent and in Combination With Pembrolizumab in Advanced or Metastatic Malignancy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Treatment-emergent adverse events (TEAEs) including determination of DLTs and serious AEs (SAEs)
研究概览
简要总结
The study of LVGN6051-201 is designed to use a bridging dose escalation to quickly establish the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) as well as the recommended Phase 2 dose(s) (RP2D) of LVGN6051, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody (Pembrolizumab) in the treatment of advanced or metastatic malignancy.
详细描述
Based on the dose escalation results from the study of LVGN6051-101, a bridging dose escalation (3+3) is used in study of LVGN6051-201. The traditional 3 + 3 dose escalation algorithm to identify the MTD and/or RDE and RP2D of LVGN6051 as a single agent (monotherapy) and in combination with pembrolizumab. The first stage of the study is the single agent dose escalation and expansion phase (Part A). The second stage of the study is the combination dose escalation and expansion phase (Part B). Patients will be considered evaluable for safety and tolerability if they receive at least one dose of LVGN6051 or pembrolizumab at the specified cohort dose. Patients in all parts of the trial will remain on therapy until confirmed disease progression or for 2 years, whichever occurs first. However, patients who are clinically unstable will discontinue following the initial assessment of disease progression
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
- •Males or females aged ≥ 18 years.
- •Ability to understand and willingness to sign a written informed consent document.
- •Patients must have a histologically or cytologically confirmed metastatic or unresectable malignancy.
- •Estimated life expectancy, in the judgment of the Investigator, of at least 90 days.
- •Adequate bone marrow, liver, and renal functions.
- •Men and women of childbearing potential must agree to take highly effective contraceptive methods.
- •Patients should recover from all reversible AEs of previous anticancer therapies to baseline.
排除标准
- •Receipt of CD137 and or PD-1 antibodies.
- •Receipt of systemic anticancer therapy within 5 half-lives of the first dose of study treatment.
- •Known active CNS metastasis and/or carcinomatous meningitis.
- •Has received a live-virus vaccine within 30 days.
- •Has had a Grade ≥ 3 allergic reaction to treatment with a monoclonal antibody.
- •Abnormality of QT interval or syndrome.
- •Patients with history of Grade ≥ 3 immune-related AEs (irAEs) or irAE.
- •Patients who are receiving an immunologically-based treatment for any reason.
- •Active or chronic autoimmune disease that has required systemic treatment in the past 2 years or who are receiving systemic therapy for an autoimmune or inflammatory disease.
- •Has a clinically significant cardiac condition, including unstable angina, acute myocardial infarction within 6 months.
- •Has an active infection requiring intravenous (i.v.) anti-infectives within 14 days before the first dose of study treatment.
- •Tested positive of HIV or HBV or HCV.
- •Female patients who are pregnant or breastfeeding.
- •Any evidence of severe or uncontrolled systemic disease.
- •Has previously had a CAR-T therapy, or stem cell or bone marrow or solid organ transplant.
研究组 & 干预措施
Monotherapy Dose Escalation
LVGN6051 monotherapy dose escalation
干预措施: LVGN6051 (Drug)
Monotherapy Dose Expansion
LVGN6051 dose expansion cohorts
干预措施: LVGN6051 (Drug)
Combination therapy dose escalation
LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose escalation
干预措施: LVGN6051 (Drug)
Combination therapy dose escalation
LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose escalation
干预措施: Pembrolizumab (Drug)
Combination therapy dose expansion
LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose expansion cohorts
干预措施: LVGN6051 (Drug)
Combination therapy dose expansion
LVGN6051 in combination with anti-PD-1 antibody pembrolizumab dose expansion cohorts
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Treatment-emergent adverse events (TEAEs) including determination of DLTs and serious AEs (SAEs)
时间窗: up to 24 months
Adverse events will be assessed, and severity will be assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
MTD or RDE or RP2D
时间窗: up to 24 months
maximal tolerated dose, recommended dose for expansion or recommended phase 2 dose
次要结局
- PK parameter Cmax(up to 24 months)
- ADA to LVGN6051(up to 24 months)
- DCR(up to 24 months)
- PK parameter AUC(up to 24 months)
- PK parameter t1/2(up to 24 months)