A First-In-Human, Multicenter, Open-Label, Phase I Dose Escalation Study To Evaluate The Safety, Tolerability And Pharmacokinetics Of YH004 As A Single Agent And Combination With Toripalimab In Subjects With Advanced Solid Tumors And Relapsed Or Refractory Non-Hodgkin Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 3
- 主要终点
- Maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D)
研究概览
简要总结
YH004 is a humanized monoclonal antibody that specifically binds to 4-1BB, and acts as an agonist against 4-1BB.
This first in human study of YH004 is designed to establish the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D) of YH004, both as a single agent (monotherapy) and in combination with a fixed dose of anti-PD-1 antibody (Toripalimab) in the treatment of advanced solid tumors and relapsed or refractory non-Hodgkin Lymphoma.
详细描述
This is an open-label, non-randomized, two-stage, FIH Phase 1 study, utilizing an accelerated dose escalation followed by a traditional 3 + 3 dose escalation algorithm to identify the MTD and/or RP2D of YH004 as a single agent (monotherapy) and in combination with Toripalimab. The first stage of the study is the dose escalation phase (i.e., Phase 1a). The second stage of the study is the dose expansion phase (i.e., Phase 1b). During the study, dose interruption(s) and/or delay(s) may be implemented based on toxicity. Dose modifications are permitted following protocol guidelines. Intra-patient dose escalations will be allowed for the early dose cohorts (single-patient dose groups) in Phase 1a. Patients will be considered evaluable for safety and tolerability if they receive at least one dose of YH004 or Toripalimab at the specified cohort dose. Patients in all parts of the trial will remain on therapy until confirmed disease progression or for 1 year, 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
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged 18 years to 80 years at the time of screening.
- •Ability to understand and willingness to sign a written informed consent document.
- •Subjects must have advanced histologically or cytologically confirmed solid tumor or relapsed or refractory Non-Hodgkin lymphoma.
- •Adequate bone marrow, liver, and renal functions.
- •Men and women of childbearing potential must agree to take highly effective contraceptive methods.
- •Women of reproductive potential must have negative serum beta human chorionic gonadotropin (β -HCG) pregnancy test within 7 days of the first dose.
排除标准
- •Receipt of systemic anticancer therapy including investigational agents or devices within 5 half-lives of the first dose of study treatment.
- •Known active CNS metastasis.
- •Has received a live-virus vaccine within 28 days.
- •History of clinically significant sensitivity or allergy to monoclonal antibodies and their excipients or known allergies to antibodies produced from Chinese hamster ovary cells.
- •Abnormality of QT interval or syndrome.
- •Patients with history of Grade ≥ 3 immune-related AEs (irAEs) or irAE.
- •Patients who receive concurrent or prior use of an immunosuppressive agent within 4 weeks of the first dose of study drug.
- •Previous exposure to anti-CD137 (eg, utomilumab, urelumab) antibodies. .
- •Active or chronic autoimmune disease that has required systemic treatment in the past 3 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 before the first dose of study treatment.
- •History of (non-infectious) pneumonitis that required corticosteroids or current pneumonitis, or history of interstitial lung disease..
- •Female patients who are pregnant or breastfeeding.
- •Any evidence of severe or uncontrolled systemic disease.
- •Any condition that the investigator or primary physician believes may not be appropriate for participating the study.
研究组 & 干预措施
YH004
The dose escalation phase includes 7 dose levels of YH004, and the highest dose is up to 10mg/kg. Route of administration is IV infusion, and the frequency of administration is once every 3 weeks (Q3W). one cycle is 3 weeks, and treatment can be up to 16 cycles if patients receive benefits.
干预措施: YH004 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D)
时间窗: up to 24 months
The MTD and/or RP2D will be determined based on TEAEs
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
次要结局
未报告次要终点