First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1029 in Patients With Malignant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Genmab
- 入组人数
- 48
- 试验地点
- 8
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of the trial is to evaluate the safety of GEN1029 (HexaBody®-DR5/DR5) in a mixed population of patients with specified solid tumors
详细描述
The trial is an open-label, multi-center first-in-human trial of GEN1029 (HexaBody®-DR5/DR5). The trial consists of two parts a dose escalation part (phase 1, first-in-human (FIH) and an expansion part (phase 2a). The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) has been determined.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Patients with advanced and/or metastatic cancer who have no available standard therapy or who are not candidates for available standard therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1029 may be beneficial.
- •Patient must be ≥ 18 years of age
- •Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
- •Have an acceptable hematological status
- •Have an acceptable renal function
- •Have an acceptable liver function
- •Have an Eastern Cooperative Oncology Group performance status of 0 or 1
- •Body weight ≥ 40kg
- •Patients both females and males, of childbearing or reproductive potential must agree to use adequate contraception from screening visit until six months after last infusion of GEN1029
排除标准
- •Acute deep vein thrombosis or clinically relevant pulmonary embolism, not stable for at least 8 weeks prior to first GEN1029 administration
- •Have clinically significant cardiac disease
- •Have uncontrolled hypertension as defined in the protocol
- •Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new (younger than 6 months) or progressive brain metastases or stroke
- •History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of Investigational Medicinal Product (IMP)
- •Have received a cumulative dose of corticosteroid ≥ 150 mg prednisone (or equivalent doses of corticosteroids) within two weeks before the first GEN1029 administration
- •History of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or suspected allergy or intolerance to any agent given in the course of this trial
- •Radiotherapy within 14 days prior to first GEN1029 administration
- •Any prior therapy with a compound targeting DR4 or DR5
- •History of chronic liver disease or evidence of hepatic cirrhosis
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From Day 1 to 28 days after the first dose of study drug
DLT criteria in the dose escalation phase of this trial are defined as hematologic toxicity including Grade (G) 4 neutropenia/thrombocytopenia for minimal duration of 7 days, G3/4 febrile neutropenia, \>=G3 thrombocytopenia with bleeding, or G4 anemia; and non-hematologic toxicity including G4 infusion-related reactions (IRR) or anaphylaxis, G3 IRR did not resolve to =\<G1 within 24 hours, \>=G3 diarrhea/vomiting (did not respond to optimal treatment within 2 days), G3 nausea (did not respond to optimal treatment within 7days), or Hy's law or protocol-specified toxicities related to liver function test results or amylase and/or lipase elevations; or any \>=G3 possibly related non-hematological AE, which occurred during first 2 cycles (as specified in protocol).
Number of Participants With >= Grade 3 Laboratory Results
时间窗: Day 1 through Day 565 (corresponding to maximum observed duration)
Number of participants with laboratory measurements of Grade \>= 3 by NCI-CTCAE v4.03 are reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE. Based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. In case a participant reported multiple severity grades for an AE, only the maximum grade was used.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: Day 1 through Day 565 (corresponding to maximum observed duration)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically important'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening during the treatment period including the safety follow-up period.
次要结局
- Volume of Distribution (Vss) at Steady State of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Maximum Observed Plasma Concentration (Cmax) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Duration of Response (DoR) According to RECIST 1.1(From Day 1 through 8.8 months (corresponding to maximum observed duration))
- Plasma Concentration of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Area Under Plasma Concentration-time Curve From Time Zero to the Time of Last Nonzero Concentration (AUC[0-Clast]) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Change From Baseline in Anti-tumor Activity Measured by Tumor Shrinkage(From Baseline (Day 1) through 8.8 months (corresponding to maximum observed duration))
- Progression-Free Survival (PFS) According to RECIST 1.1(From Day 1 through 8.8 months (corresponding to maximum observed duration))
- Area Under Plasma Concentration-time Curve From Time Zero to Infinity (AUC[0-inf]) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Total Clearance (CL) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Time to Reach Maximum Observed Concentration (Tmax) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1029(From Screening (Day -21 to -1) through Day 478 (corresponding to maximum observed duration))
- Number of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(From Day 1 through 8.8 months (corresponding to maximum observed duration))
- Half-life Lambda-z (t1/2) of Hx-DR5-01 and Hx-DR5-05(Predose, end of infusion, 2, 4, 24, 48, 168 and 336 hours after end of infusion on Day 1 of Cycles 1, 2, 3)
- Time to Response (TTR) According to RECIST 1.1(From Day 1 through 8.8 months (corresponding to maximum observed duration))
- Overall Survival (OS) According to RECIST 1.1(From Day 1 through 8.8 months (corresponding to maximum observed duration))