A Phase 1b/2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of HDM2005 in Combination With Standard of Care in Patients With Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 97
- 试验地点
- 21
- 主要终点
- Number of participants who experience dose-limiting toxicities (DLTs) in dose-escalation part
研究概览
简要总结
The purpose of this phase 1b/2 study is to evaluate the safety, tolerability, and antitumor activity of HDM2005 in combination with standard of care in participants with diffuse large B-cell lymphoma. This study will include two arms: Cohort A (HDM2005 + R-GemOx) will enroll participants with relapsed/refractory DLBCL. Cohort B (HDM2005 + R-CHP) will enroll participants with untreated DLBCL. The study will consist of two parts: dose-escalation part and dose-expansion part.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18-75 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy >12 weeks.
- •Histologically confirmed diffuse large B-cell lymphoma (DLBCL).
- •a. Cohort B: International Prognostic Index (IPI) score of 2-
- •Prior treatment:
- •Cohort A: At least one (≥1) line of prior systemic therapy.
- •Cohort B: Has received no prior treatment for DLBCL.
- •At least one bi-dimensionally measurable (≥1.5 cm) nodal lesion, or one bi-dimensionally measurable (≥1 cm) extranodal lesion, as measured on computed tomography (CT) scan.
- •Adequate organ system and hematologic function as defined in protocol.
排除标准
- •Known active central nervous system (CNS) lymphoma.
- •Prior of allogeneic hematopoietic stem cell transplantation and has acute or ongoing graft-versus-host disease (GVHD) of any grade.
- •Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •History of severe bleeding disorders.
- •History of interstitial lung disease or radiation pneumonitis.
- •Prior solid organ transplant.
- •Ongoing Grade >1 treatment-related adverse events.
- •Current or history of clinically significant cardiovascular and cerebrovascular diseases.
- •Active infection requiring systemic therapy.
- •Concurrent active HBV or HCV infection or known history of human immunodeficiency virus (HIV) infection.
- •Prior ROR1-targeted therapy.
- •Ongoing corticosteroid therapy.
- •Current active autoimmune disease or history of autoimmune disease requiring treatment.
- •History of drug anaphylaxis or severe food allergy.
- •Any history or current evidence of disease, treatment, or laboratory abnormality as determined by the investigator that may affect the study results, interfere with the subject's full participation in the study, or be contrary to the subject's best interests.
研究组 & 干预措施
Participants with r/r DLBCL (Cohort A)
Participants with r/r DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8) plus 1000 mg/ m^2 gemcitabine (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8), 100 mg/ m^2 oxaliplatin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6-8 cycles.
干预措施: Oxaliplatin (Drug)
Participants with r/r DLBCL (Cohort A)
Participants with r/r DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8) plus 1000 mg/ m^2 gemcitabine (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8), 100 mg/ m^2 oxaliplatin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6-8 cycles.
干预措施: HDM2005 (Drug)
Participants with r/r DLBCL (Cohort A)
Participants with r/r DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8) plus 1000 mg/ m^2 gemcitabine (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8), 100 mg/ m^2 oxaliplatin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6-8 cycles.
干预措施: Rituximab or Rituximab biosimilar (Drug)
Participants with r/r DLBCL (Cohort A)
Participants with r/r DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8) plus 1000 mg/ m^2 gemcitabine (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6-8), 100 mg/ m^2 oxaliplatin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6-8 cycles.
干预措施: Gemcitabine (Drug)
Participants with untreated DLBCL (Cohort B)
Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.
干预措施: HDM2005 (Drug)
Participants with untreated DLBCL (Cohort B)
Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.
干预措施: Rituximab or Rituximab biosimilar (Drug)
Participants with untreated DLBCL (Cohort B)
Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.
干预措施: Cyclophosphamide (Drug)
Participants with untreated DLBCL (Cohort B)
Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.
干预措施: Doxorubicin (Drug)
Participants with untreated DLBCL (Cohort B)
Participants with untreated DLBCL will receive a dose of HDM2005 (1.8 mg/kg or 2.0 mg/kg, on Day 2 Cycle 1 and Day 1 Cycle 2 to 6) plus 750 mg/m^2 cyclophosphamide (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), 50 mg/m^2 doxorubicin (on Day 2 Cycle 1 and Day 1 Cycle 2 to 6), and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 and 2 Cycle 1 and Day 1 Cycle 2 to 6 of each 3-week cycle for up to 6 cycles. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles.
干预措施: Prednisone (Drug)
结局指标
主要结局
Number of participants who experience dose-limiting toxicities (DLTs) in dose-escalation part
时间窗: Up to ~3 weeks
The CTCAE, Version 5.0 will be used to grade the severity of AEs in this study. DLTs will be reported for dose-escalation part of this study.
Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-escalation part
时间窗: Up to ~54 months
Incidence and grading of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) (based on the National Cancer Institute's Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0). Incidence of treatment interruption and dose adjustment due to AEs and changes in laboratory tests, vital signs, physical examination, electrocardiogram (ECG), and Eastern Cooperative Oncology Group (ECOG) performance status score.
Complete response (CR) rate in dose-expansion part
时间窗: Up to ~30 months
CR rate is defined as the percentage of participants who achieve a complete response (CR) per Lugano criteria, as determined by the investigator
RP2D of HDM2005
时间窗: Up to ~30 months
Recommended phase 2 dose of HDM2005 in combination with SoC in patients with r/r DLBCL and untreated DLBCL
次要结局
- Plasma concentration of HDM2005, total antibody and monomethyl auristatin E (MMAE)(Up to ~30 months)
- Time to response (TTR)(Up to ~54 months)
- Time to progression (TTP)(Up to ~54 months)
- Overall survival (OS)(Up to ~54 months)
- Number of participants positive for anti-drug antibodies (ADA)(Up to ~30 months)
- Number of participants who experience adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) in dose-expansion part(Up to ~54 months)
- Objective response rate (ORR)(Up to ~30 months)
- Progression-free survival (PFS)(Up to ~54 months)
- Duration of response (DOR)(Up to ~54 months)