A Phase 1 First-in-Human Study of PTK7-Directed Antibody Drug Conjugate HWK-007 in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 226
- 试验地点
- 16
- 主要终点
- Determine Maximum Tolerated Dose (MTD)
研究概览
简要总结
HWK-007-101 is a multicenter, open-label, first-in-human (FIH) Phase 1 study evaluating HWK-007, a protein tyrosine kinase 7 (PTK7)-targeted antibody drug conjugate (ADC), in adult participants with advanced or metastatic solid tumors known to be expressing PTK7. The study employs a sequential dose escalation and dose expansion design without a control group.
详细描述
The study consists of 2 phases, Phase 1a (dose escalation) and Phase 1b (dose expansion). In Phase 1a, participants with non-squamous Endothelial Growth Factor Receptor Wild type (EGFR Wt) NSCLC, platinum resistant ovarian cancer (PROC), and endometrial cancer will be enrolled. In Phase 1b, non-squamous EGFR Wt NSCLC expansion cohort(s) will be opened, based on the safety, tolerability, PK, and preliminary antitumor data in Phase 1a.
In Phase 1a of the study, HWK-007 will initially be administered as an intravenous (IV) infusion every 3 weeks (Q3W).
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
- •Have one of the following solid tumor cancers:
- •Monotherapy escalation and backfill cohorts:
- •non-squamous EGFR-Wt NSCLC
- •Endometrial carcinoma
- •Platinum Resistant Ovarian Cancer
- •Monotherapy expansion cohorts:
- •Non-squamous EGFR-Wt NSCLC
- •Additional tumor indications to be defined in a future amendment
排除标准
- •Individual with known or suspected uncontrolled central nervous system (CNS) metastases
- •Individual with history of carcinomatous meningitis
- •Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- •Individual with evidence of corneal keratopathy or history of cornea transplant
- •Any serious unresolved toxicities from prior therapy
- •Significant cardiovascular disease
- •Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms)
- •History of pneumonitis/interstitial lung disease
- •Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
研究组 & 干预措施
Dose Expansion Group 2 - 21-day treatment cycle - Tumor TBD
Expanded enrolment at second selected dose of HWK-007 administered intravenously (IV) in Tumor - TBD
干预措施: HWK-007 (Drug)
Dose Expansion Group 3 - 21-day treatment cycle - Tumor TBD
Expanded enrolment at third selected dose in Tumor - TBD
干预措施: HWK-007 (Drug)
Dose Expansion Group 4 - 21-day treatment cycle - Tumor TBD
Dose Expansion of HWK-007, a PTK7-directed ADC.
干预措施: HWK-007 (Drug)
Dose Escalation - 21 Day treatment cycle
Escalating doses of HWK-007 administered intravenously (IV)
干预措施: HWK-007 (Drug)
Dose Expansion Group 1- 21-day treatment cycle - non-squamous EGFR-WT NSCLC
Expanded enrolment at selected dose of HWK-007 in NSCLC.
干预措施: HWK-007 (Drug)
结局指标
主要结局
Determine Maximum Tolerated Dose (MTD)
时间窗: From Cycle 1, Day 1 until Cycle 1, Day 21 (21-day cycles)
Determine the highest dose of HWK-007 that can be administered without signs of toxicity measured at the end of Cycle 1 (21 day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE).
Determine Maximum Administered Dose (MAD)
时间窗: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until the MTD is reached.
Determine the highest dose administered during the dose escalation part of the study measured at the end of Cycle 1 (21 day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE).
Determine the Recommended Dose for Expansion (RDE)
时间窗: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycles) until MTD is identified.
Determine the dose that will be recommended for further study within the tumor types studied in this clinical trial measured at the end of Cycle 1 (21 day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE).
次要结局
- Characterize the Volume of Distribution (Vd) of HWK-007 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 (21-day cycles))
- Assess ADA (Anti drug antibody) against HWK-007(Every cycle from Cycle 1, Day 1 (21-day cycles) until 30 days past the last dose of study drug for up to 24 months.)
- Evaluate the Overall Response Rate (ORR)(From Cycle 1, Day 1 (21-day cycles), every 6-weeks for the first 4 assessments and then every 6 weeks for up to 24 months until disease progression or 24 months, whichever comes first.)
- Evaluate Overall Survival (OS).(From Cycle 1, Day 1 (21-day cycles) until death or 24 months, whichever comes first.)
- Maximum Concentration - Cmax of HWK-007 (ADC, total antibody, CPT116, and CPT119)(At Cycle 1 and Cycle 4 - (21-day cycles))
- Time to Maximum Concentration (Tmax) of HWK-007 (ADC, total antibody, CPT116, and CPT119)(At Cycle 1 and Cycle 4 (21-day cycles).)
- Area Under the Concentration Time Curve (AUC) for HWK-007 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 - (21-day cycles))
- T1/2 - Half-life of HWK-007 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 (21-day cycles))
- Clearance (CL)(Cycle 1 and Cycle 4 (21-day cycles))
- Evaluate the Duration of Response (DoR) to HWK-007(From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first.)
- Evaluate Progression-free Survival (PFS)(From Cycle 1, Day 1 (21-day cycles) infusion to End of Study (up to 24 months))
- Evaluate Disease control Rate (DCR)(From Cycle 1, Day 1 (21-day cycles) until disease progression or 24 months, whichever comes first.)
- Time to Response (TTR)(From Cycle 1, Day 1 (21-day cycles) until End of Study or 24 months, whichever comes first.)