A Phase 1/2, First-in-human, Multicenter Study of Emiltatug Ledadotin (Emi-Le) in Participants With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 360
- 试验地点
- 50
- 主要终点
- Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation)
研究概览
简要总结
A Study of Emi-Le in Participants with Solid Tumors
详细描述
This first-in-human (FIH) study will test the safety, side effects, and antitumor activity of a drug called Emi-Le ((Emiltatug Ledadotin, formerly XMT-1660). A side effect is anything a drug does to the body besides treating the disease.
Participants in the study will have cancer that has come back after a period of time during which the cancer could not be detected (recurrent), spread in the body near where it started (advanced) or spread through the body (metastatic).
The study will have three parts. The first part called Dose Escalation, will find out how much Emi-Le should be given to participants. The second part called Dose Expansion, will use the dose found in the first part to find out how safe Emi-Le is and if it works to treat solid tumors. The third part, the Phase 2 part of the trial, called EMBLEM-1, will find out if Emi-Le works to treat aggressive Adenoid Cystic Carcinoma and continue to check how safe Emi-Le is.
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
- •Recurrent or advanced solid tumor and has disease
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Participants in DES must have at least one measurable disease (target) lesion as defined by RECIST version 1.
- •Tumor tissue, either archival or from a fresh tumor biopsy, available for testing or be willing to undergo a minimally invasive tumor biopsy to obtain tumor tissue for local testing, if not medically contraindicated, prior to Cycle 1 Day 1
- •Brain magnetic resonance imaging (MRI) during the Screening period unless obtained within 30 days prior to Screening (based on standard clinical care), if they meet either of the following criteria:
- •All participants with TNBC
- •Participants with a history of brain metastases or with neurologic symptoms or signs suspicious for brain metastases.
排除标准
- •Prior treatment with an Antibody Drug Conjugate (ADC) containing an auristatin payload. Prior treatment with another ADC containing other payloads is allowed.
- •Major surgery within 28 days of starting study treatment, systemic anticancer therapy within the time period of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), whichever is less, or palliative radiation therapy to the chest within 3 months of starting study treatment or to other anatomic sites within 14 days of starting study treatment.
- •Diagnosis of additional malignancy that required active treatment (including surgery, systemic therapy, and radiation) within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix.
- •Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis or carcinomatous meningitis.
- •Prior B7-H4 targeted treatment.
- •History of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver diseases.
- •Current severe, uncontrolled systemic disease (e.g. clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could increase the risk of serious adverse events (SAEs) or interfere with per-protocol evaluations, in the judgment of either the Sponsor or the Investigator.
- •Clinically significant cardiovascular disease
- •Active keratitis (inflammation of the cornea of the eye)
研究组 & 干预措施
Emi-Le
Single arm Emi-Le alone (monotherapy)
干预措施: Emi-Le (Drug)
结局指标
主要结局
Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with XMT-1660 during the first cycle of treatment (Dose Escalation)
时间窗: 17 months
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of XMT-1660
Objective Response Rate (ORR) (Dose Expansion)
时间窗: approximately 3 years
The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Incidence of adverse events (Dose Escalation and Dose Expansion)
时间窗: 3 years
Assess the safety and tolerability of Emi-Le by determining the number of patients with adverse events from date of first dose to 60 days post last dose
Frequency of adverse events that are considered dose-limiting toxicities (DLTs) and associated with Emi-Le during the first cycle of treatment (Dose Escalation)
时间窗: 17 months
Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of Emi-Le
Objective Response Rate (ORR) (Dose Expansion and EMBLEM-1)
时间窗: approximately 3 years
The percentage of patients with a best overall response of complete or partial response as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
次要结局
- Assess antidrug antibodies (ADA) and neutralizing antibodies (nAB) (Dose Escalation and Dose Expansion)(3 years)
- Objective Response Rate (ORR) (Dose Escalation)(Up to approximately 3 years)
- Duration of response (DOR) (Dose Escalation and Dose Expansion)(Up to approximately 3 years)
- Maximum observed plasma concentration of XMT-1660 (Cmax) (Dose Expansion)(3 years)
- Area under the concentration-time curve of XMT-1660 (AUC) (Dose Expansion)(3 years)
- Systemic clearance of XMT-1660 (Dose Expansion)(3 years)
- Apparent terminal elimination half-life of XMT-1660 (Dose Expansion)(3 years)
- Time of maximum observed plasma concentration of XMT-1660 (Tmax) (Dose Expansion)(3 years)
- Volume of Distribution (Dose Expansion)(3 years)
- Trough concentration of XMT-1660 (Ctrough) (Dose Expansion)(3 years)
- Duration of response (DOR) (Dose Escalation, Dose Expansion, and EMBLEM-1)(Up to approximately 3 years)
- Maximum observed plasma concentration of Emi-Le and payload (Cmax) (Dose Escalation and Dose Expansion)(Up to approximately 3 years)
- Area under the concentration-time curve of Emi-Le and payload (AUC) (Dose Escalation and Dose Expansion)(Up to approximately 3 years)
- Antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) (Dose Escalation, Dose Expansion, and EMBLEM-1)(Up to approximately 3 years)
- Assess the overall survival (OS) of patients treated with Emi-Le (Dose Escalation, Dose Expansion, and EMBLEM-1)(Up to approximately 3 years)
- Incidence of adverse events (EMBLEM-1)(3 years)
- Progression-free survival (PFS) (EMBLEM-1)(Up to approximately 3 years)