A Phase I/II Study Evaluating the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP） in Previously Untreated Patients With CD20-positive DLBCL
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Part I: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD)
研究概览
简要总结
This trial is a multicenter, open-label, single-arm, dose-escalation and dose-expansion clinical trial. The dose was increased according to the "3 + 3" rule. Patients with previously untreated patients with CD20-positive DLBCL were selected to evaluate the safety, tolerance (DLT, MTD), pharmacokinetics, and anti-tumor activity of TRS005 in combination with standard doses of cyclophosphamide, doxorubicin, and prednisone（T-CHP） by intravenous drip every 3 weeks.
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
- •Part I: Age 18 -65 years old; Part II: Aged ≥ 18 years old, both male and female.
- •Previously untreated patients with CD20-positive DLBCL diagnoses by 2022 WHO.
- •Measurable disease of at least 15mm (node)/10mm (extranodal).
- •ECOG performance status 0-
- •International Prognostic Index (IPI) score of 2-
- •Estimated survival time ≥6 months.
- •Having sufficient organ function.
- •Female and male patients of childbearing age and their spouses are willing to carry out adequate contraception throughout the study period, and female patients of childbearing age must have negative serum pregnancy test within 7 days before the first administration.
- •Patients voluntarily agree to participate in the study and to sign the informed consent form.
排除标准
- •Contraindication to any of the individual components of study drugs, including prior receipt of xenoproteins, biological agents.
- •Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load; Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load; Human immunodeficiency virus (HIV) seropositive.
- •Clinically apparent central nervous system (CNS) lymphoma.
- •Patient has ≥ Grade 2 peripheral neuropathy.
- •Investigator-assessed diabetes uncontrolled by drug therapy.
- •Clinically significant third space fluid accumulation.
- •Patients with other malignancies within the past 5 years.
- •With active autoimmune diseases.
- •Accompanied by serious cardiovascular diseases.
- •Accompanied by serious diseases and serious active infections.
- •The dosage of steroid hormone (prednisone phase equivalent) used greater than 20mg/ day within 28 days prior to first administration for more than 14 consecutive days, or immunosuppressive treatment.
- •Various vaccines were inoculated within 28 days prior to first administration;
- •Major surgery (except diagnostic biopsy) within 28 days prior to first administration or during the study period.
- •Participate in clinical trials of other drugs or medical devices within 28 days prior to first administration.
- •Serious medical or psychiatric illness likely to interfere with participation in this study.
- •Investigators assessed as unsuitable to participate in this study for other reasons.
研究组 & 干预措施
TRS005+CHP
TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP）
干预措施: TRS005 (Drug)
TRS005+CHP
TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP）
干预措施: Cyclophosphamide (Drug)
TRS005+CHP
TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP）
干预措施: Doxorubicin (Drug)
TRS005+CHP
TRS005 in Combination With Cyclophosphamide, Doxorubicin, and Prednisone（T-CHP）
干预措施: Prednisolone (Drug)
结局指标
主要结局
Part I: Dose Limiting Toxicities (DLTs) and Maximum Tolerated Dose (MTD)
时间窗: Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21)
All dose-escalation cohorts will consist of at least 3 participants. If a DLT is observed in 1 participant at a given dose level during the DLT observation period before dose escalation, additional participants will be enrolled at that dose level for a total of at least 6 participants. DLT assessment forms part of determining the Maximum Tolerated Dose (MTD). The highest dose level resulting in DLTs in less than one-third of a minimum of 6 participants will be declared the MTD.
Part I and II: Adverse Events
时间窗: Day 1 up to approximately 6 months
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 5.0 (NCI-CTCAE, v5.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).
次要结局
- Overall Response Rate (ORR)(At the end of treatment (Month 6))
- Duration of Response (DOR)(Up to 24 months)
- Progression-Free Survival (PFS)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Immunogenicity(At the end of treatment (Month 6))
- Serum concentration(At the end of cycle 4 (each cycle is 21 days))