A Phase 1 Multiple Dose Study to Evaluate the Safety and Tolerability of XmAb819 in Subjects With Relapsed or Refractory Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Xencor, Inc.
- 入组人数
- 307
- 试验地点
- 26
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of XmAb®819 administered intravenous (IV) or subcutaneous (SC) in subjects with relapsed or refractory clear cell renal cell carcinoma and to identify the minimum safe and biologically active dose and the recommended dose (RD).
详细描述
This is a Phase 1, multicenter, open-label, multiple-dose study designed in 2 parts: dose escalation, and dose expansion. The study is designed to establish the dosing schedule of XmAb819 administered IV and the dosing schedule of XmAb819 administered SC. The study is designed to evaluate safety and tolerability; to assess PK/PD and immunogenicity; and to preliminarily assess antitumor activity of XmAb819 in subjects with ccRCC and other solid tumors. All eligible subjects will have relapsed or refractory disease after standard therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Subjects must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the local site investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •Subjects who have relapsed and refractory ccRCC, pRCC, NSCLC, and CRC with evidence of disease progression on standard-of-care therapies
- •ECOG performance status of 0 or
- •All subjects must have adequate tumor sample available (slides or archival FFPE blocks)
排除标准
- •Prior treatment with an investigational anti-ENPP3/CD203c therapy
- •History of serious allergic or anaphylactic/hypersensitivity reaction to monoclonal antibody therapy
- •Systemic antineoplastic therapy within 5 half-lives on the first dose of study treatment.
- •Failure to recover from any clinically significant toxicity related to previous anticancer treatment
- •Have known active central nervous system metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable,
- •Active known autoimmune disease (except that subjects are permitted to enroll if they have vitiligo; type 1 diabetes mellitus; residual hypothyroidism due to an autoimmune condition that is treatable with hormone replacement therapy only; psoriasis, atopic dermatitis, or another autoimmune skin condition that is managed without systemic therapy; or arthritis that is managed without systemic therapy beyond oral acetaminophen and nonsteroidal anti-inflammatory drugs)
- •Evidence of any serious infection requiring IV anti-infective treatment within 14 days prior to the first dose of study drug
- •Have a known additional malignancy that is progressing or has required active treatment within the past 2 years
研究组 & 干预措施
Dose Escalation and Expansion
Dose Escalation will establish the dosing schedule for XmAb819 administered IV and the dosing schedule of XmAb819 administered SC. The dosing schedule includes the priming dose, step-up priming dose(s), the minimum safe and biologically active dose.
Dose Expansion may administer XmAb819 IV, and XmAb819 SC.
干预措施: XmAb819 (Biological)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: 28 days
Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the optimal dose regimen.
Incidence of treatment-emergent adverse events (safety and tolerability of XmAb819)
时间窗: 28 days
Safety and tolerability as assessed by incidence of TEAEs; incidence of clinically significant changes in safety laboratory tests, PE findings, vital signs, and ECGs; incidence and severity of CRS
次要结局
- Measurement of AUCtau(56 days)
- Objective Response rate(42 days)
- Progression-free survival(42 days)
- Measurement of Cmax(56 days)
- Duration of response(42 days)