A Phase 1 Study of TJ011133 Administered Alone or in Combination With Pembrolizumab or Rituximab in Subjects With Relapsed/Refractory Advanced Solid Tumors and Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 98
- 试验地点
- 19
- 主要终点
- Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
研究概览
简要总结
The purpose of this study is to assess the safety and tolerability of TJ011133 in participants with solid tumors and lymphoma.
详细描述
This is an open-label, multi-center, multiple dose, Phase 1 study to evaluate the safety, tolerability, maximum tolerated dose (MTD) or maximum administered dose (MAD), pharmacokinetic (PK), pharmacodynamic, and recommended Phase 2 dose (RP2D) of TJ011133, an anti-CD47 antibody, in participants with advanced relapsed or refractory solid tumors and lymphoma. The study will be conducted in 2 parts. Part 1 comprises a single agent dose escalation (Part 1A) and 2 separate combination therapy dose escalations (Part 1B with pembrolizumab and Part 1C with rituximab) and Part 2 includes a dose expansion study.
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
- •Part 1: Participants with advanced relapsed/refractory solid tumors and lymphoma.
- •Part 2 with Rituximab: Participants with diffuse large B-cell lymphoma (DLBCL) or Indolent B-cell Lymphoma, with at least one measurable lesion by Lugano and available fresh metastatic biopsy sample prior to study entry.
- •Part 2 with Pembrolizumab: Participants with locally advanced non-small-cell lung carcinoma (NSCLC) with disease progression or immune-oncology treatment naive Epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer, with at least one measurable lesion defined by Response Elevation Criteria in Solid Tumors (RECIST) 1.1, and available fresh metastatic biopsy prior to study entry.
- •All Parts: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1 and adequate bone marrow, renal, and liver functions.
排除标准
- •Participants with known symptomatic central nervous system tumors or known central nervous system metastases or leptomeningeal disease requiring steroids. Participants who document stable and central nervous system metastases and are off steroids for more than 4 weeks may be enrolled in the study.
- •Participants with Burkitt's lymphoma, lymphoblastic lymphoma, Richter's transformation, primary effusion lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma.
- •Participants with mantle cell lymphoma.
- •Impaired cardiac function or clinically significant cardiac diseases.
- •Prior treatment with CD47 or SIRPα inhibitors.
- •Prior autologous stem cell transplant <=3 months prior to starting study.
- •Prior allogeneic stem cell transplant with either standard or reduced intensity conditioning.
- •Prior chimeric antigen receptor or chimeric antigen receptor T-cell therapy.
- •History of autoimmune anemia or autoimmune thrombocytopenia.
- •Positive Direct Antiglobulin Test.
- •Active graft versus host disease (GVHD) or ongoing immunosuppression for GVHD.
研究组 & 干预措施
Part 1A - TJ011133 Monotherapy
TJ011133 alone will be administered at up to 7 dose levels (0.3, 1, 3, 10, 20, 30, 45 mg/kg) once weekly (Q1W) (the 0.3 mg/kg dose level cohort will be enrolled if a DLT in 1 out of 3 subjects is observed following the 1 mg/kg dose level).
干预措施: TJ011133 (Drug)
Part 1B - Combination therapy of TJ011133 with pembrolizumab
TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.
干预措施: TJ011133 (Drug)
Part 1B - Combination therapy of TJ011133 with pembrolizumab
TJ011133 will be administered Q1W, starting at 20 mg/ kg, in combination with pembrolizumab.
干预措施: Pembrolizumab (Drug)
Part 1C - Combination therapy of TJ011133 with rituximab
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.
干预措施: TJ011133 (Drug)
Part 1C - Combination therapy of TJ011133 with rituximab
TJ011133 will be administered Q1W, starting at 20 mg/kg, in combination with rituximab.
干预措施: Rituximab (Drug)
Part 2 - Dose Expansion
30 participants (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 participants with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
干预措施: TJ011133 (Drug)
Part 2 - Dose Expansion
30 participants (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 participants with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
干预措施: Pembrolizumab (Drug)
Part 2 - Dose Expansion
30 participants (with DLBCL or indolent lymphoma) in the TJ011133 combination therapy with rituximab expansion and 20 participants with solid tumors in the TJ011133 combination therapy with pembrolizumab expansion.
干预措施: Rituximab (Drug)
结局指标
主要结局
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status
时间窗: up to 100 days post last dose
Change in Eastern Cooperative Oncology Group (ECOG) Performance Status.
Dose Limiting Toxicities (DLT)
时间窗: 21 or 28 days, depending on study part
Part 1A DLT period is 3 weeks, Part 1B DLT period is 3 weeks, Part 1C DLT period is 4 weeks.
Incidence and Severity of Adverse Events
时间窗: up to 100 days post last dose
The CTCAE criteria will be used to assess adverse events on this trial.
Maximum Tolerated Dose (MTD) for Both Monotherapy and Combination Therapy
时间窗: 21 or 28 days, depending on study part
Based on DLT definitions.
次要结局
- PK: Area Under the Curve From Time Zero To The Time Of The Last Quantifiable Concentration (AUC0-t)(up to 100 days post last dose)
- PK: Maximum Observed Concentration (Cmax)(up to 100 days post last dose)
- PK: Trough Concentration (Ctrough)(up to 100 days post last dose)
- PK: Volume Of Distribution (Vz)(up to 100 days post last dose)
- Efficacy: Overall Survival (OS)(up to 100 days post last dose)
- Efficacy: Best Overall Response (BOR)(up to 100 days post last dose)
- Pharmacokinetic (PK): Area Under the Curve From Time Zero To Infinity (AUC∞)(up to 100 days post last dose)
- PK: Terminal Elimination Half-Life (T1/2)(up to 100 days post last dose)
- PK: Volume of Distribution at Steady State (Vss)(up to 100 days post last dose)
- Efficacy: Objective Response Rate (ORR)(up to 100 days post last dose)
- PK: Time of the Maximum Observed Concentration (Tmax)(up to 100 days post last dose)
- PK: Clearance (CL)(up to 100 days post last dose)
- PK: AUC Over A Dosing Interval (AUCtau)(up to 100 days post last dose)
- Immunogenicity: Anti-drug antibodies (ADA)(up to 100 days post last dose)
- Efficacy: Duration Of Response (DOR)(up to 100 days post last dose)
- Efficacy: Progression-Free Survival (PFS)(up to 100 days post last dose)