An Open-label, Multicenter Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of FG-M131 in Patients With TRBC1-positive Relapsed/Refractory Peripheral T-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
FG-M131 for injection is an antibody-drug conjugate (ADC) targeting the T-cell receptor beta chain constant region 1 (TRBC1). TRBC1 is a subunit of the αβ T-cell receptor (TCR) complex. Targeting TRBC1 can eliminate TRBC1-positive malignant T cells while sparing TRBC2-positive normal T cells, providing a novel strategy for the treatment of T-cell malignancies.
This study is a multicenter, open-label Phase I/II clinical trial in patients with TRBC1-positive relapsed/refractory peripheral T-cell lymphoma, designed to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity of FG-M131 for injection in this patient population. The study consists of a Phase I dose-escalation stage and a Phase IIa cohort-expansion stage.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily sign the informed consent form, understand the study, are willing to comply with and have the ability to complete all trial procedures;
- •Age 18-75 years (inclusive), any gender;
- •Histologically and/or cytologically confirmed peripheral T-cell lymphoma or cutaneous T-cell lymphoma;
- •Relapsed or refractory lymphoma after at least one prior line of therapy；
- •Able to provide tumor tissue specimens;
- •ECOG performance status of 0 or 1;
- •Expected survival ≥3 months;
- •Have at least one measurable tumor lesion;
- •Adequate cardiac, bone marrow, liver, renal function;
排除标准
- •Have received a live vaccine within 3 months prior to the first dose;
- •Have received radiotherapy within 4 weeks prior to the first dose;
- •Have received other anti-tumor drug therapy within 3 weeks or within 5 half-lives of the anti-tumor drug prior to the first dose;
- •Have undergone major surgery within 4 weeks prior to the first dose;
- •Have previously received any therapy targeting the TRBC1 antigen or any antibody-drug conjugate with MMAE payload;
- •Have received autologous stem cell transplantation within 3 months prior to the first dose;
- •Have previously received allogeneic stem cell transplantation;
- •Have a history of other malignancies within 5 years prior to the first dose;
- •Have received high-dose systemic vitamin A therapy (daily dose >15,000 IU [i.e., 5,000 mcg]) within 3 weeks prior to the first dose of study drug;
- •Have any condition requiring systemic treatment with corticosteroids (>20 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose;
- •Have received oral retinoid drugs for any indication within 3 weeks prior to the first dose;
- •Have adverse reactions from prior treatments that have not recovered to CTCAE v5.0 Grade ≤1 (excluding alopecia and anemia) prior to the first dose;
- •Presence or history of central nervous system lymphoma, leptomeningeal disease, or spinal cord compression;
- •Have a history of severe allergic reactions or are allergic to the investigational drug;
- •Have experienced a clinically significant cardiac disease within 6 months before the first dose;
- •Have uncontrolled systemic diseases assessed by the investigator, including diabetes, hypertension, pulmonary fibrosis, interstitial lung disease, etc.;
- •Known history of Hepatitis C or chronic active Hepatitis B;
- •Clinically uncontrolled diseases such as diabetes mellitus, thyroid disease, or other severe systemic diseases requiring systemic treatment;
- •Active or progressive infection requiring systemic therapy within 2 weeks prior to the first dose;
- •Known or suspected active autoimmune disease requiring systemic therapy within 2 years prior to the first dose;
- •Are pregnant or breastfeeding;
研究组 & 干预措施
FG-M131 Dose Expansion Cohort
Once the effective dose has been determined, 2 expansion cohorts will be opened to evaluate the efficacy and safety of the selected dose.
干预措施: FG-M131 (Drug)
FG-M131 Dose Escalation Cohort
Dose Escalation Cohort Eight dose levels of FG-M131 will be tested according to an accelerated titration method followed by a adaptive BOIN design.
干预措施: FG-M131 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: 21 days
MTD
Objective Response Rate (ORR)
时间窗: Up to 24 months
ORR is defined as the proportion of participants who have a best overall response of Complete Response (CR) or Partial Response (PR) as assessed by investigator evaluation.
Complete Response Rate (CRR)
时间窗: Up to 24 months
CRR is defined as the proportion of participants who have a best overall response of Complete Response (CR) as assessed by investigator evaluation
Safety assessed by Adverse Events (AEs)
时间窗: Up to 24 months
Incidence and severity of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
次要结局
- Progression Free Survival (PFS)(Up to 24 months)
- Duration Of Response (DOR)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Maximum measured plasma concentration of FG-M131(Up to 24 months)
- Time to maximum plasma concentration of FG-M131(Up to 24 months)
- Half-life of FG-M131(Up to 24 months)
- ADA(Up to 24 months)