A First-in-Human (FIH), Multicenter, Open-Label, Phase 1 Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of YH002 in Subjects With Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose (MTD)
研究概览
简要总结
This is an open-label, dose-escalation study of the study drug YH002. The study is designed to determine the safety, tolerability and maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of YH002 in patients with advanced solid Malignancies
详细描述
This is a single arm clinical trial in subjects with advanced solid tumor receiving multiple doses of YH002 intravenously (IV). YH002 will be administered (IV) in 6-48 patients with advanced solid tumors. An accelerated titration method followed by a traditional 3+3 dose escalation algorithm will be utilized to determine MTD/MAD. Patients will be dosed at Dose A, Dose B, Dose C, Dose D, Dose E, Dose F, Dose G, and Dose H every 3 weeks (Q3W).
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
- •Male or female, aged ≥ 18 years
- •Confirmed as histologically or cytologically, locally advanced or metastatic non-resectable solid tumors, must have received and progressed on, or been ineligible for, or intolerant of available standard therapies known to confer clinical benefit or for whom no standard therapy exits
- •Subjects enrolled in Dose D, Dose E, Dose F, Dose G, and Dose H cohorts must have at least one measurable lesion per RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1 and life expectancy no less than 3 months
- •Recovery, to Grade 0-1, from adverse events related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy
排除标准
- •Symptomatic central nervous system (CNS) metastases. Subjects with asymptomatic CNS metastases who are radiologically and neurologically stable ≥ 4 weeks following CNS- directed therapy, and do not require corticosteroids or anticonvulsants are eligible for study entry
- •Received anticancer therapy or radiation therapy within 5 half-lives or 4 weeks prior to study entry, whichever is shorter
- •Received palliative radiotherapy to a single area of metastasis within 2 weeks prior to study entry
- •Received agonist antibodies to TNFR such as anti-CD137, OX40, CD27 and CD357 antibodies prior to the study entry
- •Allergy or sensitivity to YH002, or known allergies to antibodies produced from Chinese hamster ovary cells which assessed to increase the potential for an adverse hypersensitivity to YH002 by Investigator
- •History of a Grade 3-4 allergic reaction to treatment with another monoclonal antibody
- •Grade ≥3 irAEs or irAEs that lead to discontinuation of prior immunotherapy. Hypothyroidism, Type 1 DM, and dermatologic irAEs (except previous Steven Johnson Syndrome, toxic epidermal necrolysis, or other severe forms of dermatitis). Type 1 DM should be controlled with reduction of toxicity to Grade 1 or less
- •Concomitant active autoimmune disease or history of autoimmune disease requiring systemic treatment or history of autoimmune disease within 2 years prior to study entry (except vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy)
- •Received steroids or other immunosuppressive systemic therapy within 4 weeks prior to the first dose of the study drug, or has need to be treated during the study (except using on low systemic absorption location prevent or treat non- autoimmune condition)
- •Active hepatitis B or C. Hepatitis B carriers without active disease or cured Hepatitis C may be enrolled
- •Severe cardiovascular disease within 6 months of study entry
研究组 & 干预措施
YH002
All subject will receive YH002 intravenously as single agent every three weeks (Q3W) for up to 2 years, until intolerable toxicity, confirmed disease progression, withdrawal of consent, or Investigator decision, whichever comes first. Subjects who remain on treatment in the absence of disease progression for more than 2 years may continue to receive study drug through a single patient IND.
干预措施: YH002 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD)
时间窗: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
MTD is defined as the highest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycle
Dose-limiting toxicities (DLT)
时间窗: Cycle 1 of each cohort. Duration of one cycle is 3 weeks
DLT is defined as a toxicity (adverse event at least possibly related to YH002) occurring during the DLT observation period (the initial 21 days)
Number of participants with adverse events and serious adverse events
时间窗: From screening up to 2 year
The safety profile of YH002 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
次要结局
- Area under the serum concentration versus time curve within one dosing interval (AUCtau)(Up to 2 years)
- Volume of distribution at steady state (Vss)(Up to 2 years)
- Time to reach maximum serum concentration (Tmax)(Up to 2 years)
- Dose proportionality(Up to 2 years)
- Duration of response (DOR)(Up to 2 years)
- Disease control rate (DCR)(Up to 2 years)
- Duration of disease control (DOC)(Up to 2 years)
- Trough concentration before the next dose is administered (Ctrough)(Up to 2 years)
- Terminal half-life (T1/2)(Up to 2 years)
- Incidence of anti-drug antibodies (ADAs)(Up to 2 years)
- Volume of distribution (Vd)(Up to 2 years)
- Clearance (CL)(Up to 2 years)
- Incidence of neutralizing antibodies (NAbs)(Up to 2 years)
- Objective response rate (ORR)(Up to 2 years)
- Progression free survival (PFS)(Up to 2 years)
- Time to response (TTR)(Up to 2 years)
- Maximum serum concentration (Cmax)(Up to 2 years)