A Phase 1, First-in-Human, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of XmAb®662 in Monotherapy or in Combination With Pembrolizumab in Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Xencor, Inc.
- 入组人数
- 7
- 试验地点
- 5
- 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 evaluate the safety, tolerability, and pharmacokinetics of intravenous administration of XmAb662 monotherapy or in combination with pembrolizumab in subjects with advanced solid tumors and to identify the recommended dose regimen that is safe and biologically effective for XmAb662.
详细描述
This is a first-in-human (FIH), Phase 1, open-label, multicenter dose escalation study with cohort expansion at one or more recommended dose(s) (RDs), designed to evaluate the safety and tolerability of XmAb662 monotherapy or in combination with pembrolizumab in subjects with selected solid tumors that have progressed after standard/approved therapies, or for which there are no effective available therapies. This study will be conducted in 2 parts: dose escalation (Part 1) and dose expansion (Part 2), and subdivided into arms for XmAb662 monotherapy and XmAb662+pembrolizumab combination.
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
- •Advanced, recurrent or metastatic solid malignancy that is not amenable to curative-intent treatment and which has progressed after standard therapy appropriate for the following tumor type: Head and neck squamous cell carcinoma, melanoma, non-small cell lung cancer, small cell lung cancer (SCLC), urothelial carcinoma, colorectal cancer, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, endometrial cancer, cutaneous squamous cell carcinoma, breast cancer, ovarian cancer (epithelial), castration-resistant prostate cancer (adenocarcinoma)
- •Measurable disease by RECIST 1.1; subjects with prostate cancer who have evaluable disease according to PCWG3 criteria may enroll
- •Life expectancy of at least 3 months
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •For dose escalation cohorts, subjects must have adequate archival tumor sample or willing to provide a fresh tumor
- •Adequate organ function
排除标准
- •Receiving treatment with the following therapies: Interleukin (IL)-12 either alone or as part of a treatment regimen; checkpoint inhibitors given within 4 weeks of study drug; other anticancer therapies, including chemotherapy or radiation therapy, given within 4 weeks of the start of study drug (palliative radiation given within a 1-week washout is allowed)
- •History of allergic or anaphylactic/hypersensitivity reaction to immunotherapy
- •History of a life-threatening (Grade 4) immune-related adverse event (irAE) related to prior immunotherapy or any prior irAE, regardless of grade
- •History or evidence of any clinically unstable/uncontrolled disorder, condition, or disease (including, but not limited to, cardiopulmonary, renal, metabolic, hematologic, or psychiatric) other than their primary malignancy
- •Known active central nervous system involvement by malignant disease; subjects with previously treated brain metastases may participate provided they are radiologically and clinically stable
- •For subjects receiving pembrolizumab, prior Grade 3 or Grade 4 infusion-related reactions to pembrolizumab, or known hypersensitivity to pembrolizumab
- •Other protocol defined inclusion/exclusion criteria apply
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: First 3 weeks on treatment for each subject]
Safety and tolerability as assessed by incidence of DLTs and all available data which will be used to determine the recommend dose(s)
Incidence and severity of treatment emergent adverse events (TEAEs)
时间窗: Up to 2 years
Safety and tolerability as assessed by incidence of TEAEs, including clinically significant changes in safety laboratory tests and clinical findings
次要结局
- Progression-free survival(Up to 2 years)
- Duration of response(Up to 2 years)
- Characterization of pharmacokinetics(56 Days)
- Objective response rate(Up to 2 years)