A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-tumor Activity of JMT108 Injection in Participants With Advanced Malignant Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 270
- 试验地点
- 2
- 主要终点
- Number of participants with Dose Limiting Toxicities as assessed by NCI CTCAE v5.0 (excluding cytokine release syndrome, CRS).
研究概览
简要总结
The goal of this clinical trial is to test JMT108, a type of drug called a bispecific antibody in adult patients with locally advanced or metastatic solid tumors.
The main questions it aims to answer are:
- To assess the safety and tolerability of JMT108 at increasing doses and determine the dose and schedule to be used in the second part of the study (Phase 1a)
- To assess effectiveness of JMT108 in participants with locally advanced or metastatic tumors (Phase 1b)
- To evaluate how quickly JMT108 is metabolized by the body (pharmacokinetics or PK)
- To evaluate if antibodies to the study drug develop (immunogenicity)
- To evaluate preliminary efficacy to the drug
- To explore the pharmacodynamic (PD) characteristics of JMT108
- To explore the correlation between biomarker levels and preliminary efficacy
Participants will:
- Provide written informed consent
- Undergo screening tests to ensure they are eligible for study treatment
- Attend all required study visits and receive JMT108 by intravenous injection every 2 weeks until the study doctor determines study treatment should be stopped, based on how well a participant is doing on treatment
- Be followed for progression every 3 months for up to 2 years
详细描述
This Phase 1 study is a single agent, 2-part (including dose escalating and expansion) study conducted in patients with locally advanced or metastatic solid tumors who are unresponsive or intolerant to all standard of care or have no standard of care available.
Dose escalation (Phase 1a) - Dose escalation will be conducted using a BOIN design.
In the dose-escalation phase, a total of 4 dose levels-0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, and 2 mg/kg-will be sequentially escalated. The BOIN design is adopted for the dose-escalation part of this study to determine the MTD. The target toxicity rate for the MTD is 0.3, and the maximum sample size for the dose-escalation BOIN design is 30 participants. Participants are enrolled to receive treatment in cohorts of size 3. Dose escalation and de-escalation decisions are made based on the occurrence of DLTs within the DLT observation window.
After thorough evaluation by the SMC, one or more dose levels may be added between the highest escalated dose level and the next lower dose level for better DLT assessment.
The dose escalation phase includes a screening period (D-28 to D-1), a treatment period, an end of treatment (EOT) visit, and a follow-up period.
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
- •Major Inclusion Criteria:
- •Age ≥18 years
- •Participants with histologically or cytologically confirmed locally advanced or metastatic solid tumors who are unresponsive or intolerant to all standard of care or have no standard of care available
- •At least one evaluable tumor lesion according to RECIST v1.
- •ECOG performance status score ≤
- •Expected survival ≥ 3 months
排除标准
- •Active central nervous system metastases and/or leptomeningeal metastases
- •AEs from prior therapy which have not recovered to Grade ≤1 or baseline as per NCI CTCAE v5.0
- •Prior therapy
- •Any other unapproved investigational drugs or treatments within 4 weeks prior to the first dose of the investigational drug (C1D1).
- •Chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, or other anti-tumor therapies within 4 weeks prior to the first dose of the investigational drug, except in the following situations:
- •Nitrosoureas or mitomycin C within 6 weeks prior to the first dose of the investigational drug;
- •Use of oral fluoropyrimidines and small-molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first dose of the investigational drug;
- •Use of herbal medicine/products with anti-tumor indications within 2 weeks prior to the first dose of the investigational drug.
研究组 & 干预措施
Phase 1a Dose Escalation
In the dose escalation phase, dose escalation will be conducted using a BOIN design. A total of 4 dose levels-0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, and 2 mg/kg-will be sequentially escalated.
干预措施: JMT108 (Drug)
Phase 1a Dose Expansion
During the dose escalation process, dose expansion and/or exploration of different dosing frequencies (e.g., Q3W) will be conducted for the dose level that the SMC evaluates as safe/ tolerable and where anti-tumor activity is also observed.
干预措施: JMT108 (Drug)
Phase 1b Cohort Expansion
Participants may be enrolled in the cohort expansion study with tumor types including but not limited to Cohort 1: lung cancer, Cohort 2: colorectal cancer, Cohort 3: hepatic cancer, Cohort 4: gastric cancer, Cohort 5: melanoma and Cohort 6: other malignant tumors (including cervical cancer, renal cancer, bile duct cancer, squamous cell head and neck cell cancer, etc.). Based on the results of Phase 1a, the SMC will discuss and determine the administration dose and frequency for the cohort expansion study. If necessary, several different doses/frequencies may be selected for cohort expansion.
干预措施: JMT108 (Drug)
结局指标
主要结局
Number of participants with Dose Limiting Toxicities as assessed by NCI CTCAE v5.0 (excluding cytokine release syndrome, CRS).
时间窗: through study completion, an average of 1 year
To evaluate the safety and tolerability of JMT108 to determine the dose and schedule to be used in phase 1b.
Number of participants with Tumor Response as assessed by RECIST version 1.1 criteria
时间窗: through study completion, an average of 1 year
To evaluate preliminary efficacy of JMT108 injection as monotherapy in participants with advanced malignant tumors.
次要结局
- JMT108 Pharmacokinetics: Area under the concentration time curve over the dosing interval(through study completion, an average of 1 year)
- JMT108 Pharmacokinetics: Elimination half-life (t1/2)(through study completion, an average of 1 year)
- JMT 108 Pharmacokinetics: Clearance (CL)(through study completion, an average of 1 year)
- JMT108 Objective response rate (ORR)(through study completion, an average of 1 year)
- JMT108 Immunogenicity: Number of participants with anti-drug-antibody (ADA)(through study completion, an average of 1 year)