NCT05322408已完成1 期
A Phase I Study of HCW9218, a Bifunctional TGF-B; Antagonist/IL-15 Protein Complex, in Select Advanced Solid Tumors After Failing at Least Two Prior Therapies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- The Primary Objective of the Dose Finding Component is to Determine the Maximum Tolerated Dose (MTD) of HCW9218
研究概览
简要总结
This is a single center, Phase I dose finding study of HCW9218 for the treatment of advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers). HCW9218 is a novel bi-functional fusion protein complex administered by subcutaneous (SC) injection. It is comprised of a soluble fusion of two human TGFβRII domains, human tissue factor, and human IL-15, and a second soluble fusion of two human TGFβRII domains and a sushi domain of human IL-15Rα. HCW9218 activates IL-15R signaling on effector immune cells and the dimeric TGFβRII functions as a "trap" for all three human TGF-β isoforms.
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
- •Histologically or cytologically confirmed advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers), has failed at least 2 prior lines of therapy given either in the recurrent or metastatic setting and must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- •Measurable disease per RECIST v 1.
- •Acute effects of any prior therapy must have resolved to baseline or Grade ≤1 NCI CTCAE v5 except for AEs not constituting a safety risk by enrolling Investigator judgment.
- •Age 18 years or older at the time of consent.
- •ECOG Performance Status 0 or
- •Evidence of adequate organ function within 14 days prior to enrollment as defined in Section 4.1.
- •Adequate pulmonary function with PFTs >50% FEV1 if symptomatic or known impairment.
- •Sexually active persons of child-bearing potential or with partners of childbearing potential must agree to use a highly effective form of contraception (refer to Section 4.1.10 for acceptable methods) for at least 28 days after the last dose of HCW
- •Provides voluntary written consent prior to the performance of any research related activity.
排除标准
- •Pregnant or breastfeeding.
- •History of clinically significant vascular disease, including any of the following within 6 months prior to start of study treatment: MI or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease.
- •Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval greater or equal to 470 milliseconds by Fridericia's correction).
- •Known or suspected untreated CNS metastases.
- •Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start.
- •Other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease-free for 3 years after surgical treatment.
- •Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
- •Prior therapy with TGF-β antagonist, IL-15 or analogs.
- •Concurrent use of St. John's wort and and/or other herbal CYP modulators within 7 days of Day
- •Must agree to not use during study treatment through the end of treatment visit to be eligible.
- •Known autoimmune disease requiring active treatment. Persons with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
- •Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
- •Prior organ allograft or allogeneic transplantation.
- •Known HIV-positive or AIDS.
- •Psychiatric illness/social situations that would limit compliance with study requirements.
- •Other illness or a medical issue that in the opinion of the Investigator would exclude the subject from participating in this study
研究组 & 干预措施
Administer HCW9218
Experimental
Administer HCW9218 as monotherapy at assigned dose by SC injection once every 3 weeks. Dose Level
-1 - 0.1 mg/kg
- - (start) 0.25 mg/kg
- - 0.5 mg/kg
- - 0.8 mg/kg
- - 1.2 mg/kg
干预措施: HCW9218 (Drug)
结局指标
主要结局
The Primary Objective of the Dose Finding Component is to Determine the Maximum Tolerated Dose (MTD) of HCW9218
时间窗: through study completion, an average of 12 months
Given that little to no toxicity is expected, the MTD will be determined using an adaptation of the continual reassessment method (CRM) (O'Quigley, 1996) starting with 1 patient cohorts.
次要结局
- Estimate Response Rate (Complete Response (CR), Partial Response (PR) or Stable Disease (SD)(12 months after 1st dose)
- Estimate Progression of Overall Survival (OS)(1 year after 1st dose)
- Estimate Progression Free Survival (PFS)(1 year after 1st dose)
研究者
研究点 (1)
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