A Phase 1, First-in-Human, Dose Escalation and Expansion, Multicenter Study of XMT-2056 in Participants With Advanced/Recurrent Solid Tumors That Express HER2
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 57
- 试验地点
- 28
- 主要终点
- Frequency of dose-limiting toxicities (DLTs) associated with XMT-2056 during the first cycle of treatment (Dose Escalation)
研究概览
简要总结
A Study of XMT-2056 in advanced/recurrent solid tumors that express HER2.
详细描述
The first-in-human (FIH) study of XMT-2056 is a Phase 1, open-label study of XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2. The XMT-2056 monotherapy trial will consist of dose escalation (DES) and expansion (EXP) parts.
DES will be the dose-finding portion of the study to assess the safety and tolerability of XMT-2056 and determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 Dose (RP2D). The RP2D will be determined based on the totality of the clinical data, including safety and preliminary anti-tumor effect, PK, and relevant biomarker data.
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
- •Participant has recurrent or metastatic solid tumors with HER2 expression and has disease progression after treatment, is intolerant to treatment, or is contraindicated with available anti-cancer therapies known to confer benefit, based on investigator's judgement. Note: Participants must have HER2 positivity per the results of their most recent tumor tissue testing, defined as IHC 3+ or IHC 2+ in combination with in situ hybridization (ISH)+. Participants with ERBB2-activating mutations or ERBB2 gene amplification in the absence of HER2 positivity are considered ineligible.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Participant must have measurable disease as defined by RECIST version 1.
- •Participant has fresh tumor biopsy tissue available for submission to central laboratory. If obtaining fresh tumor tissue is medically contraindicated, archival tumor tissue can be submitted following written approval of the request by the study Medical Monitor. Samples must be obtained after the participant's most recent HER2-targeting therapy unless determined to be medically contraindicated after discussion with the medical monitor.
排除标准
- •• Participant is receiving immunosuppressive doses of systemic medications, (doses >10 mg/day prednisone or equivalent) that cannot be discontinued for at least 2 weeks before the first dose and during study drug treatment administration. Note: physiologic hormone replacement therapy is an exception.
- •Participant has received prior treatment targeting STING pathway.
- •Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within the last 2 years, expect for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the breast or the cervix. Participants with an additional malignancy that has a low risk for recurrence may be eligible after discussion with the study Medical Monitor.
- •Participants have untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.
- •Participants are eligible if CNS metastases are adequately treated and participants are neurologically stable for at least 2 weeks prior to enrollment.
- •In addition, participants must be either off corticosteroids, or on a stable/decreasing dose of ≤ 10 mg prednisone daily (or equivalent).
研究组 & 干预措施
XMT-2056
XMT-2056 alone (monotherapy)
干预措施: XMT-2056 (Drug)
结局指标
主要结局
Frequency of dose-limiting toxicities (DLTs) associated with XMT-2056 during the first cycle of treatment (Dose Escalation)
时间窗: 15 months
Determine the maximum tolerated dose (MTD) of XMT-2056
Incidence of adverse events (Dose Escalation and Dose Expansion)
时间窗: 3 years
Assess the safety and tolerability of XMT-2056 by determining the number of patients with adverse events from date of first dose to 30 days post last dose.
Objective Response Rate (ORR) (Dose Expansion)
时间窗: 3 years
The percentage of patients with a best overall response of confirmed complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Area under the concentration-time curve of XMT-2056 (AUC) (Dose Escalation and Dose Expansion)(3 years)
- Time of maximum observed plasma concentration of XMT-2056 (Tmax) (Dose Escalation and Dose Expansion)(3 years)
- Systemic clearance of XMT-2056 (Dose Escalation and Dose Expansion)(3 years)
- Disease control rate (DCR) (Dose Escalation and Dose Expansion)(3 years)
- Maximum observed plasma concentration of XMT-2056 (Cmax) (Dose Escalation and Dose Expansion)(3 years)
- Objective Response Rate (ORR) (Dose Escalation)(3 years)
- Duration of response (DOR) (Dose Escalation and Dose Expansion)(3 years)
- Volume of Distribution (Dose Escalation and Dose Expansion)(3 years)
- Serum samples for analysis of XMT-2056 antidrug and neutralizing antibodies (ADA/nAb) (Dose Escalation and Dose Expansion)(3 years)
- Apparent terminal elimination of half-life of XMT-2056 (Dose Escalation and Dose Expansion)(3 years)
- Trough concentration of XMT-2056 (Ctrough) (Dose Escalation and Dose Expansion)(3 years)