A Phase 1, Multicenter, Open-label, First-in-human, Dose Escalation and Expansion Study of DM005 in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- DM005
- 疾病 / 适应症
- Carcinoma, Non-Small-Cell Lung
- 发起方
- Doma Biopharmaceutical（Suzhou）Co., Ltd.
- 入组人数
- 136
- 试验地点
- 6
- 主要终点
- Dose-limiting Toxicities (DLTs) of DM005
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
The goal of this clinical trial is to find out about the safety, efficacy, and tolerability of DM005 for patients with the advanced solid tumors. DM005 is an experimental drug which is not approved by health authorities for the treatment of advanced solid tumors. For each participant, there will be a screening period of up to 28 days, a treatment period consisting of 21-day cycles, an end of treatment (EOT) Visit (+7 days), and a Follow-up Visit at 30 days (±7 days) after the EOT Visit.
Participants with advanced solid malignant tumors will be treated with DM005 on Day 1 of each cycle (every 3 weeks, Q3W). An initial dose of DM005 will be infused intravenously (IV) into each participant for approximately 60 minutes (±10) on Cycle1 Day 1. If there is no infusion-related reaction (IRR) during or after the initial dose, with the Investigator's confirmation and supervision, the subsequent dosing of DM005 in the following cycles maybe infused IV for approximately 30 minutes ( ±5). A 21-day observation period (Cycle 1) will then occur, at the end of which all relevant safety data will be reviewed.
详细描述
This first-in-human (FIH), multicenter, open-label, dose escalation and dose expansion study is to evaluate the safety, preliminary efficacy and pharmacokinetic (PK) characteristics of DM005 monotherapy in participants with advanced solid tumors. DM005, a bispecific ADC developed using fully human antibodies with a common light chain, which targets c-MET and EGFR. Subjects with solid malignant tumors will be treated with DM005 on Day 1 once Q3W (dose adjustments may be required depending on the safety profile and PK data of each dose
研究者
入排标准
入选标准
- •Common inclusion criteria for both Parts
- •Participants must have the ability to understand and willingness to sign a written informed consent document.
- •Participants who have pathologically or cytologically documented metastatic/advanced NSCLC, gastroesophageal cancer, CRC, HCC, pancreatic cancer, or HNSCC, not curable with standard local therapies (i.e., surgery and/or radiation) and have progressed on standard therapy, or intolerant to standard therapy.
- •Participants must be ≥18 years of age on the day of signing the informed consent form (ICF).
- •Participants must have an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to
- •Has a life expectancy ≥3 months.
- •Has measurable disease based on response evaluation criteria in solid tumors (RECIST) version 1.1.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Participants have another active invasive malignancy within 5 years, with the following exceptions and notes:
- •History of noninvasive malignancy, such as cervical cancer in situ, in situ melanoma, or ductal carcinoma in situ of the breast that is in complete remission years after treatment with curative intent is allowed.
- •Malignancies with a negligible risk of metastasis or death (such as adequately treated basal or squamous cell skin cancer and localized prostate cancer).
- •Current or history of hematologic malignancy.
- •Anticancer therapy (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-cancer therapies, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogs, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter, prior to the first study dose. Radiotherapy with a wide field of radiation within 28 days, or radiotherapy with a limited field of radiation for palliation within 14 days of the first study dose. Major surgery, other than diagnostic surgery, within 4 weeks of the first study dose.
- •Primary central nervous system (CNS) malignancies or CNS metastases. Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (\>20 mg prednisone or equivalent) for at least 4 weeks.
- •Presence of bulky disease (defined as any single mass \>7 cm in its greatest dimension). Individuals with a mass \>7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.
- •Has an uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
- •Has clinically significant corneal disease.
研究组 & 干预措施
Dose Level 3
≤2 mg/kg
干预措施: DM005
Dose Level 6
≤8 mg/kg
干预措施: DM005
Dose Level 1
0.5mg/kg
干预措施: DM005
Dose Level 2
≤1 mg/kg
干预措施: DM005
Dose Level 4
≤4 mg/kg
干预措施: DM005
Dose Level 5
≤6 mg/kg
干预措施: DM005
结局指标
主要结局
Dose-limiting Toxicities (DLTs) of DM005
时间窗: 12 months
Incidence of DLTs of DM005 will be determined. A dose-limiting toxicity (DLT) was defined as grade 3 neurological toxicities (e.g. chemical meningitis) or other grade 4 toxicity.
Maximum tolerated dose (MTD) for DM005
时间窗: 12 months
The MTD of DM005 will be determined. The MTD was defined as the dose where 0/3 or 1/6 patients experienced a DLT with at least two patients encountering DLT at the higher dose.
次要结局
- Maximum (peak) plasma concentration (Cmax, ng/mL)(12 months)
- Time to maximum (peak) concentration (Tmax, h)(12 months)
- Objective response rate (ORR)(12 months)
- The MTD of DM005 will be determined. The MTD was defined as the dose where 0/3 or 1/6 patients experienced a DLT with at least two patients encountering DLT at the higher dose.(12 months)
- Trough concentration (Ctrough, ng/mL)(12 months)