A Phase 1/2, Open-label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of YH32367 in Patients With HER2-Positive Locally Advanced or Metastatic Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- YH32367
- 疾病 / 适应症
- HER2-Positive Solid Tumor
- 发起方
- Yuhan Corporation
- 入组人数
- 147
- 试验地点
- 32
- 主要终点
- Treatment-emergent adverse events (TEAEs) up to Day 21
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
This first-in-human study will be counducted to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of YH32367 in Patients with HER2-Positive Locally Advanced or Metastatic Solid Tumors.
详细描述
YH32367, a novel HER2/4-1BB bispecific antibody (BsAb), simultaneously targets HER2 and h4-1BB and binds to both targets. YH32367 exhibits a strong 4-1BB signal activation as well as blocking of HER2 signaling in HER2-expressing tumor cells. YH32367 stimulates IFN-γ secretion from T cells and thereby induces tumor cells lysis. This is a Phase 1/2, open-label, multicenter, first-in-human study of YH32367. This 2-part study will include both a Dose Escalation part, to identify the Maximum Tolerated Dose (MTD) and/or two dose levels for RP2D selection, and a Dose Expansion part, to determine RP2D and to confirm the safety, tolerability and efficacy of YH32367 at the RP2D.
研究者
入排标准
入选标准
- •\[Dose Escalation Part\]
- •Pathologically confirmed HER2-positive
- •Mandatory provision of tumor tissue sample
- •\[Dose Expansion Part\]
- •Patients who have at least one measurable lesion
- •Mandatory provision of tumor tissue sample
- •Cohort 1: Pathologically confirmed HER2-positive biliary tract cancer
- •Cohort 2: Pathologically confirmed HER2-positive metastatic solid tumor malignancy other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer
排除标准
- •Uncontrolled central nervous system (CNS) metastases
- •Spinal cord compression
- •Carcinomatous meningitis
- •Acute coronary syndromes
- •Heart failure
- •Interstitial lung disease (ILD)
- •Pneumonitis
- •History of a second primary cancer
- •Human immunodeficiency virus (HIV)
- •Active chronic hepatitis B
研究组 & 干预措施
YH32367
Dose Escalation Part: 8 Cohorts. In Dose Escalation part, patients are assigned to receive YH32367 at a starting dose and the dose being escalated/de-escalated in adjacent dose cohorts. Dose Expansion Part: 2 Cohorts (Cohort 1: Biliary tract cancer, Cohort 2: Solid tumors). Dose Expansion part will consist of multiple cohorts in patients who were treated with at least 1 prior gemcitabine- and/or cisplatin-based therapy, HER2 positive biliary tract cancer(Cohort 1); in patients who were treated with all available standard therapies and have no available options, HER2 positive solid tumor malignancies other than breast and gastric or gastroesophageal junction adenocarcinoma and biliary tract cancer(Cohort 2).
干预措施: YH32367
结局指标
主要结局
Treatment-emergent adverse events (TEAEs) up to Day 21
时间窗: in dose escalation part, an average of 21 days
To assess the safety and tolerability of YH32367
Objective Response Rate (ORR)
时间窗: through dose expansion part completion, approximately 2.5 year
To assess the ORR of YH32367 at the recommended Phase 2 dose (RP2D) according to RECIST v1.1 by blinded independent central reviews (BICR)
次要结局
- Area under the serum concentration-time curve from time 0 to the last quantifiable concentration (AUClast)(up to 66 weeks)
- maximum observed serum concentration (Cmax)(up to 66 weeks)
- time to reach Cmax (Tmax)(up to 66 weeks)
- Presence and characterization of YH32367 ADA in serum including titer of ADA and neutralizing antibodies(through study completion, approximately 3.5 year)
- Objective Response Rate (ORR)(through study completion, approximately 3.5 year)
- Duration of Response (DoR)(through study completion, approximately 3.5 year)
- Disease Control Rate (DCR)(through study completion, approximately 3.5 year)
- Depth of Response(through study completion, approximately 3.5 year)
- Time to Response(through study completion, approximately 3.5 year)
- Progression-free survival (PFS)(through study completion, approximately 3.5 year)
- TEAEs(through dose expansion part completion, approximately 2.5 year)
- Overall Survival (OS)(through study completion, approximately 3.5 year)