A Phase 1 First-in-Human Study of MUC16-Directed Antibody Drug Conjugate HWK-016 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
- 265
- 试验地点
- 19
- 主要终点
- Determine Maximum Tolerated Dose (MTD)
研究概览
简要总结
HWK-016-101 is a multicenter, open-label, first-in-human (FIH) Phase 1 study evaluating HWK-016, a targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors. The study employs a dose escalation and dose expansion design without a control group.
The study consists of 2 parts (Part A: monotherapy and Part B: combination therapy with bevacizumab); each part has 2 phases, Phase 1a (dose escalation) and Phase 1b (dose expansion). Enrollment to Part A (Phase 1a and Phase 1b) will include ovarian and endometrial cancers. Enrollment to Part B (Phase 1a and Phase 1b) will include ovarian cancer only. A subsequent protocol amendment may evaluate additional tumor types.
详细描述
HWK-016-101 is a Phase 1 study evaluating HWK-016, a mucin-16 (MUC-16) targeted antibody-drug conjugate (ADC) in adult participants with advanced or metastatic solid tumors.
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, backfill and expansion cohorts:
- •Endometrial Carcinoma
- •Ovarian Cancer
- •Combination Escalation, Backfill and Expansion Cohorts a. Ovarian Cancer
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
Part A - Dose Expansion Group 2 - 21-day treatment cycle - Tumor TBD
Expanded enrolment at Recommended Dose for Expansion 2 in Ovarian Cancer
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part A - Dose Expansion Group 3 - 21-day treatment cycle - Tumor TBD
Expansion of enrolment at RDE 1 or 2 in Tumor TBD
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part B - Dose Expansion Cohort 1- 21 Day cycles of HWK-016 in combination with Bevacizumab
Expanded enrolment at RDE of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Ovarian cancer
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part B - Dose Expansion Cohort 2 - 21 Day cycles of HWK-016 in combination with Bevacizumab
Expanded enrolment at RDE of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Tumor TBD
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part B - Dose Expansion Cohort 2 - 21 Day cycles of HWK-016 in combination with Bevacizumab
Expanded enrolment at RDE of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Tumor TBD
干预措施: Bevacizumab (Drug)
Part B - Dose Escalation - 21 Day treatment cycles of HWK-016 in combination with Bevacizumab
Escalating doses of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Ovarian cancer
干预措施: Bevacizumab (Drug)
Part B - Dose Expansion Cohort 1- 21 Day cycles of HWK-016 in combination with Bevacizumab
Expanded enrolment at RDE of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Ovarian cancer
干预措施: Bevacizumab (Drug)
Part A - Dose Expansion Group 1 - 21-day treatment cycle - Tumor TBD
Dose Optimization of Recommended dose for expansion 1
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part A - Dose Escalation - 21 Day treatment cycles
Escalating doses of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV)
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part B - Dose Escalation - 21 Day treatment cycles of HWK-016 in combination with Bevacizumab
Escalating doses of HWK-016, a MUCIN-16-targeted ADC administered intravenously (IV) combined with Bevacizumab (IV) in Ovarian cancer
干预措施: HWK-016, MUCIN-16-targeted ADC (Drug)
Part A - Dose Expansion Group 4 - 21-day treatment cycle - Tumor TBD
Expansion of enrolment at RDE 1 or 2 in Tumor TBD
干预措施: HWK-016, MUCIN-16-targeted ADC (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-016 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). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
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 of HWK-016 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). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer
Determine Recommended Dose For Expansion (RDE)
时间窗: From Cycle 1, Day 1 to Cycle 1, Day 21 (21-day cycle) until MTD is identified.
Determine the dose of HWK-016 that will be recommended for further study within the tumor types studied in this clinical trial, measured at the end of Cycle 1, Day 21 (21-day cycle) by: Incidence and severity of Adverse Events (AE). Incidence of Dose-Limiting Toxicities (DLT). Incidence of Serious Adverse Events (SAE). Evaluate the safety and tolerability of HWK-016 at the selected RDE(s) determined from Phase 1a, as monotherapy (Part A) in participants with ovarian and endometrial cancers and in combination therapy with bevacizumab (Part B) in participants with ovarian cancer.
次要结局
- Area Under the Concentration Time Curve (AUC) for HWK-016 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 - (21-day cycles)
- Characterize the Volume of Distribution (Vd) of HWK-016 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 (21-day cycles))
- Maximum Concentration - Cmax of HWK-016 (ADC, total antibody, CPT116, and CPT119)(At Cycle 1 and Cycle 4 - (21-day cycles))
- Time to Maximum Concentration (Tmax) of HWK-016 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 - (21-day cycles))
- T1/2 - Half-life of HWK-016 (ADC, total antibody, CPT116, and CPT119)(Cycle 1 and Cycle 4 - (21-day cycles))
- Clearance (CL)(Cycle 1 and Cycle 4 (21-day cycles))
- Assess ADA (Anti drug antibody) against HWK-016(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.)
- Evaluate the Duration of Response (DoR) to HWK-016(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) infusion to End of Study (up to 24 months)
- Time to Response (TTR)(From Cycle 1, Day 1 (21-day cycles) until End of Study or 24 months, whichever comes first)