A Phase I/II Study of IMCnyeso, HLA- A*0201-Restricted, NY-ESO-1- and LAGE-1A-specific Soluble T Cell Receptor and Anti-CD3 Bispecific Molecule, in HLA-A*0201 Positive Patients With Advanced NY-ESO-1 and/or LAGE - 1A Positive Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 12
- 主要终点
- Phase 1: Number of Participants With Dose-limiting Toxicities
研究概览
简要总结
IMCnyeso is a bispecific fusion protein designed for the treatment of cancers that express NY-ESO-1 and/or LAGE-1A. This was a first-in-human trial designed to evaluate the safety and efficacy of IMCnyeso in HLA-A*02:01-positive adult participants whose cancer is positive for NY-ESO-1 and/or LAGE-A1.
详细描述
This was planned to be a multi-center, open label, dose finding Phase 1/2 study of single agent IMCnyeso administered in participants with NY-ESO-1 and/or LAGE-A1 positive tumors. The primary objective of the dose escalation phase (Phase 1) was to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of IMCnyeso in participants with advanced solid tumors. Preliminary efficacy was to be evaluated in Phase 2. The study was terminated early (prior to initiation of Phase 2) by the Sponsor as a strategic decision (not based on any safety signal).
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
- •HLA-A*0201 positive
- •NY-ESO-1 and/or LAGE-1A positive tumor
- •ECOG PS 0 or 1
- •Selected advanced solid tumors
- •Relapsed from, refractory to, or intolerant of standard therapy
- •If applicable, must agree to use highly effective contraception
排除标准
- •Symptomatic or untreated central nervous system metastasis
- •Inadequate washout from prior anticancer therapy
- •Significant ongoing toxicity from prior anticancer treatment
- •Impaired baseline organ function as evaluated by out-of-range laboratory values
- •Clinically significant cardiac disease
- •Active infection requiring systemic antibiotic therapy
- •Known history of human immunodeficiency virus (HIV)
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •Ongoing treatment with systemic steroids or other immunosuppressive therapies
- •Significant secondary malignancy
- •Pregnancy or lactation
研究组 & 干预措施
Phase 1: Dose Escalation
Four fixed-dose, dose escalation cohorts (Cohorts 1 to 4) and 3 intrapatient dose escalation cohorts (Cohorts 5 to 7) to establish the MTD/RP2D of IMCnyeso.
干预措施: IMCnyeso (Drug)
Phase 2: Dose Expansion
Three planned cohorts treated at the RP2D to make a preliminary assessment of the anti-tumor activity of IMCnyeso. Phase 2 was not initiated and data were not collected.
干预措施: IMCnyeso (Drug)
结局指标
主要结局
Phase 1: Number of Participants With Dose-limiting Toxicities
时间窗: Up to 35 months
Dose-limiting toxicities were defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug that occurs within the evaluation period, from the first dose up until Day 28 after the first dose
Phase 1: Number of Participants With Adverse Events
时间窗: Up to 35 months
Treatment-emergent adverse events are defined as any adverse event (AE) that started after the first dose of study drug up to 30 days after last dose of study drug, including abnormal laboratory values, vital signs, or electrocardiogram results. AE severity is graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Phase 2: Best Overall Response (BOR)
时间窗: Up to 35 months
Best overall response per RECIST v.1.1
Phase 1: Number of Participants With No Dose Interruptions or Reductions
时间窗: Up to 35 months
Tolerability of study treatment was assessed by summarizing the number of participants with no treatment dose interruptions and dose reductions
次要结局
- Phase 2: Number of Participants With No Dose Interruptions or Reductions(Up to 35 months)
- Number of Participants With Anti-IMCnyeso Antibody Formation(Up to 35 months)
- Phase 1: Number of Participants With Best Overall Response (BOR)(Up to 35 months)
- Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Measurable Concentration (AUC0-last)(Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15)
- Phase 2: Number of Participants With Adverse Events(Up to 35 months)
- Phase 1 and Phase 2: Progression-free Survival(Up to 35 months)
- Phase 1 and Phase 2: Duration of Response(Up to 35 months)
- Phase 1 and Phase 2: Overall Survival(Up to 35 months)
- Maximum Observed Plasma Drug Concentration After Single Dose Administration (Cmax)(Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15)
- Time to Reach Maximum Plasma Concentration (Tmax)(Predose and 1, 2, 4, 6, 8, and 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 15)