An Open-Label, Multicenter, Phase 1/2 Trial of GEN3014 (HexaBody®-CD38) in Relapsed or Refractory Multiple Myeloma and Other Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Genmab
- 入组人数
- 130
- 试验地点
- 66
- 主要终点
- Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The drug that will be investigated in the study is an antibody, GEN3014. Since this is the first study of GEN3014 in humans, the main purpose is to evaluate safety. In addition to safety, the study will determine the recommended GEN3014 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN3014. GEN3014 will be studied in relapsed (disease has returned) or refractory (resistant to treatment) multiple myeloma (also known as RRMM) and other blood cancers. The study consists of 3 parts:
- The Dose Escalation will test increasing doses of GEN3014 to identify a safe dose level to be tested in the other two parts.
- Expansion Part A will further test the GEN3014 dose determined from the Dose Escalation.
- Expansion Part B will compare intravenous (IV) GEN3014 with the subcutaneous (SC) daratumumab in ex-US countries.
Participants will receive either GEN3014 into the vein or daratumumab under the skin; none will be given placebo. The study duration will be different for the individual participants. Overall, the study may be ongoing up to 5 years after the last participant's first treatment.
详细描述
This trial will be conducted in 3 parts: Dose Escalation (phase 1), Expansion Parts, A and B (phase 2).
In the dose escalation phase GEN3014 will be evaluated in RRMM and relapsed and refractory acute myeloid leukemia (R/R AML). The participants will receive GEN3014 administered at various dose levels in 28-day cycles. Dose Limiting Toxicities (DLTs) will be assessed during the first treatment cycle and the Maximum Tolerated Dose (MTD) and/or Recommended phase 2 dose (RP2D) will be determined.
In Expansion Part A, GEN3014 will be further evaluated in 4 cohorts: anti-CD38 monoclonal antibody (mAb)-naive RRMM, anti-CD38 mAb-refractory RRMM, relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), and R/R AML at the RP2D identified from the Dose Escalation. In Expansion Part B, GEN3014 IV will be compared to daratumumab SC, head-to-head (H2H) to evaluate whether GEN3014 may be more potent in anti-CD38 mAb-naïve RRMM participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GEN3014
Experimental: GEN3014 Participants in Dose Escalation phase with
- RRMM
- R/R AML
Participants in Expansion Part A with
- RRMM (anti-CD38 mAb-naïve)
- RRMM (anti-CD38 mAb-refractory)
- R/R DLBCL
- R/R AML
Participants in Expansion Part B with
• RRMM (anti-CD38 mAb-naïve)
干预措施: GEN3014 (Biological)
Daratumumab
Participants in Expansion Part B with
- RRMM (anti-CD38 mAb-naïve)
干预措施: Daratumumab (Drug)
结局指标
主要结局
Dose Escalation: Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Up to 28 days during the first cycle (cycle =28 days)
To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) to be studied in the Expansion part. DLT will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.
Dose Escalation: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From first dose until the end of the safety follow-up period (30 days after last dose; up to 8 years)
Expansion Part A: Objective Response Rate (ORR) of GEN3014
时间窗: Up to 8 years
ORR is defined as the percentage of participants with a partial response (PR), or better based on International Myeloma Working Group (IMWG) criteria for MM participants, based on Lugano criteria for DLBCL participants, and based on International Working Group (IWG) response criteria for AML participants.
Expansion Part B: Objective Response Rate (ORR) of GEN3014 IV vs Daratumumab SC in Anti-CD38 mAb-naive RRMM Participants
时间窗: Up to 8 years
ORR is defined as the percentage of participants with a PR, or better based on IMWG criteria.
次要结局
- Dose Escalation: Maximum (peak) Plasma Concentration (Cmax) of GEN3014(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Dose Escalation: Pre-dose (trough) Concentrations (Ctrough) of GEN3014(Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days) (Up to 8 years))
- Dose Escalation: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Dose Escalation: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Dose Escalation: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014(From first dose until treatment discontinuation (Up to 8 years))
- Dose Escalation: Objective Response Rate (ORR) of GEN3014(Up to 8 years)
- Dose Escalation: Clinical Benefit Rate (CBR) of GEN3014(Up to 8 years)
- Dose Escalation: Duration of Response (DOR) of GEN3014(Up to 8 years)
- Dose Escalation: Time-to-response (TTR) of GEN3014(Up to 8 years)
- Dose Escalation: Progression-free survival (PFS) of GEN3014(Up to 8 years)
- Dose Escalation: Overall Survival (OS) of GEN3014(Up to 8 years)
- Expansion Part A: Clinical Benefit Rate (CBR) of GEN3014(Up to 8 years)
- Expansion Part A: Duration of Response (DOR) of GEN3014(Up to 8 years)
- Expansion Part A: Time-to-response (TTR) of GEN3014(Up to 8 years)
- Expansion Part A: Progression-free survival (PFS) of GEN3014(Up to 8 years)
- Expansion Part A: Overall Survival (OS) of GEN3014(Up to 8 years)
- Expansion Part A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0(From first dose until the end of the safety follow-up period (30 days after last dose) (Up to 8 years))
- Expansion Part A: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014(From first dose until treatment discontinuation (Up to 8 years))
- Expansion Part A: Maximum (peak) Plasma Concentration (Cmax) of GEN3014(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Expansion Part A: Pre-dose (trough) Concentrations (Ctrough) of GEN3014(Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days) (Up to 8 years))
- Expansion Part A: Area Under the Concentration Time Curve From Zero to Last Quantifiable Sample (AUC0-last)(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Expansion Part A: Area Under the Concentration Time Curve From Zero to 168 hours (AUC0-168 h)(Predose and postdose at multiple timepoints up to Cycle 6 (Cycle length=28 days); Pre-dose and 5 minutes post end of infusion from Cycle 7 and beyond (Up to 8 years))
- Expansion Part B: Ctrough Levels of GEN3014 IV or Daratumumab SC on Cycle 3 Day 1(Cycle 3 Day 1 (cycle = 28 days))
- Expansion Part B: Very Good Partial Response (VGPR), or better of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Complete Response (CR) or better of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Duration of Response (DOR) of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Time-to-response (TTR) of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Progression-free Survival (PFS) of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Overall Survival (OS) of GEN3014 IV vs Daratumumab SC(Up to 8 years)
- Expansion Part B: Time to Next Therapy (TTNT)(Up to 8 years)
- Expansion Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) per CTCAE Version 5.0(From first dose until the end of the safety follow-up period (30 days after last dose) (Up to 8 years))
- Expansion Part B: Number of Participants with Anti-Drug Antibody (ADA) of GEN3014 and Anti-daratumumab Antibodies(From first dose until treatment discontinuation (Up to 8 years))