A Phase 1/2, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of YH32364 in Patients With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 5
- 主要终点
- Treatment-emergent adverse events (TEAEs) including dose limiting toxicities (DLTs)
研究概览
简要总结
This is a study for people with locally advanced or metastatic cancer for whom previous treatment was not successful. Adults aged 18 and over with advanced cancer with Epidermal Growth Factor Receptor (EGFR) overexpressing can join the study. The purpose of this study is to find out whether a medicine called YH32364 helps people with locally advanced or metastatic cancers with EGFR overexpression.
详细描述
YH32364 is a new type of immunotherapy called a bispecific antibody that targets both Epidermal Growth Factor Receptor (EGFR) and 4-1BB. EGFR is a gene involved in cancer growth, and many cancer treatments aim to target it. 4-1BB, an immune-modulating protein, plays an important role in boosting T cell activity to combat cancer.
YH32364 is a treatment designed to activate 4-1BB specifically in tumors, aiming to avoid the liver-related side effects seen with previous 4-1BB treatments. It also helps block EGFR signals, assumed to make EGFR-targeted therapies more effective by overcoming resistance.
This study is consists of two parts. In Part 1, participants will be assigned sequentially to one of six dose levels, ranging from the lowest to the highest dose as determined by the sponsor, in order to identify an appropriate dosage.
In Part 2, participants will be randomly assigned to one of the two optimal dose levels identified in Part 1 to confirm the recommended dose.
The YH32364 will be administered via intravenous (IV) infusion once every two weeks. Participants will be required to visit the study site regularly for treatment and assessments. During all the visits, the doctors check participants' health and take note of any unwanted effects.
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
- •Must sign an informed consent form (ICF) prior to any study specific procedures
- •ECOG performance status 0 or 1
- •Estimated life expectancy of at least 3 months
- •A woman must not be breastfeeding
- •Have at least one measurable lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline ≥10 mm in the longest diameter (except lymph nodes which must have a short axis of ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), are suitable for accurate repeated measurements.
- •[Dose Escalation Only] Locally advanced or metastatic EGFR overexpressing solid tumor* that is refractory or intolerable on all available standard therapy and that is considered uncurable by local therapy
- •* One of the following pathologically confirmed EGFR overexpressing (IHC3+ or IHC2+) tumors.
- •Head and neck squamous cell carcinoma (HNSCC)
- •Non-small cell lung cancer (NSCLC): squamous cell carcinoma (SqCC)
- •Esophageal squamous cell carcinoma (ESCC)
- •Biliary tract cancer (BTC)
- •Uterine cervical cancer
- •Vulvar cancer
- •Urothelial cancer
- •Squamous cell carcinoma of other origin of tumor (e.g., skin squamous cell tumor)
- •[Dose Expansion Only] Cohort 1: Pathologically confirmed EGFR overexpressing (IHC3+ or IHC2+), locally advanced or metastatic HNSCC other than nasopharyngeal carcinoma (NPC)* that is refractory or intolerable on all available standard therapy and that is considered uncurable by local therapy.
排除标准
- •Known uncontrolled central nervous system (CNS) metastases, spinal cord compression, and/or carcinomatous meningitis
- •Have history of a second primary cancer with the exception of
- •curatively treated non-melanomatous skin cancer
- •curatively treated cervical or breast carcinoma in situ, or
- •other malignancy with no known active disease present and no treatment administered during the last 2 years
- •Have history of or current Class II, III or IV heart failure as defined by the New York Heart Association (NYHA)
- •Have history of acute coronary syndromes, including myocardial infarction, coronary artery bypass graft, unstable angina, coronary angioplasty or stenting within past 24 weeks
- •Have history of (non-infectious) interstitial lung disease (ILD) or pneumonitis that required steroids, or any evidence of current ILD or pneumonitis
- •Have autoimmune disease that has required systemic treatment
- •Infection with human immunodeficiency virus (HIV)
- •Active chronic hepatitis B or chronic hepatitis C
- •[Prior/Concomitant Therapy]
- •Have received systemic steroid therapy
- •Previous treatment with a 4-1BB/CD137-modulating agent
- •Have used a live vaccine within 4 weeks
- •Have received treatment with immunotherapy, biological therapies, targeted small molecules, or hormonal therapies
- •Have received radiation therapy
- •Have received cytotoxic chemotherapy
研究组 & 干预措施
YH32364
Dose Escalation Part: Dose Escalation part is designed to assess the safety and tolerability of YH32364 and to identify the Maximum Tolerated dose (MTD) and/or two dose levels for recommended dose (RD) selection.
Dose Expansion Part: Dose Expansion part will consist of multiple cohorts by cancer types. Cohort 1 will be initiated to determine the RD after completion of Part 1. The RD will be determined among two dose levels investigated in Cohort 1 based on the totality of available data including PK, biomarkers, dose-response, safety, and efficacy.
干预措施: YH32364 (Drug)
结局指标
主要结局
Treatment-emergent adverse events (TEAEs) including dose limiting toxicities (DLTs)
时间窗: Study Day 1 to Study Day 28 (during the DLTs evaluation period)
To assess the safety and tolerability of YH32364 in order to determine maximum tolerated dose (MTD) and select doses for dose optimization
Objective Response Rate (ORR)
时间窗: through dose expansion part completion, approximately 1.5 year
To assess the ORR of YH32364 at the recommended dose (RD) according to RECIST v1.1 by Investigator assessment
次要结局
- Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(through study completion, approximately 2.5 year)
- AUC from time 0 to infinity (AUCinf)(through study completion, approximately 2.5 year)
- Maximum observed serum concentration (Cmax)(through study completion, approximately 2.5 year)
- Time to reach Cmax (Tmax)(through study completion, approximately 2.5 year)
- Apparent terminal elimination half-life (t1/2)(through study completion, approximately 2.5 year)
- Total clearance (CL)(through study completion, approximately 2.5 year)
- Volume of distribution (Vd)(through study completion, approximately 2.5 year)
- Volume of distribution at steady state (Vss)(through study completion, approximately 2.5 year)
- AUC during dosing interval at steady state (AUCtau)(through study completion, approximately 2.5 year)
- Cmax at steady state (Cmax,ss)(through study completion, approximately 2.5 year)
- Time to reach Cmax,ss (Tmax,ss)(through study completion, approximately 2.5 year)
- Accumulation ratio (Rac)(through study completion, approximately 2.5 year)
- Trough (predose) serum concentration on Cycle 4 (Ctrough)(through study completion, approximately 2.5 year)
- Titer of YH32364 ADA(through study completion, approximately 2.5 year)
- Presence and characterization of YH32364 ADA including neutralizing antibodies(through study completion, approximately 2.5 year)
- Objective Response Rate (ORR)(through dose escalation part completion, approximately 1 year)
- Duration of Response (DoR)(through study completion, approximately 2.5 year)
- Disease Control Rate (DCR)(through study completion, approximately 2.5 year)
- Depth of Response(through study completion, approximately 2.5 year)
- Time to Response(through study completion, approximately 2.5 year)
- Progression-free survival (PFS)(through study completion, approximately 2.5 year)
- TEAEs(through dose expansion part completion, approximately 1.5 year)
- Overall Survival (OS)(through dose expansion part completion, approximately 1.5 year)