A Phase 1/2, Multicenter, Open-Label, Multi-Cohort, First-in Human Trial of DS3790a, a DXd-ADC Targeting CD37, for Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 420
- 试验地点
- 8
- 主要终点
- Number of Participants Reporting Dose-limiting Toxicities, Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Deaths in Participants With Hematological Malignancies
研究概览
简要总结
This clinical trial is designed to assess the safety, preliminary efficacy, and pharmacokinetics (PK) of DS3790a monotherapy and combination regimens in participants with hematological malignancies.
详细描述
DS3790a may be effective in the treatment of patients with hematological malignancies. The primary objective of this study will assess the safety and preliminary efficacy of DS3790a monotherapy and combination regimens.
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
- •To be eligible to participate in this trial, an individual must meet all the following criteria:
- •Sign and date the ICF, prior to the start of any trial-specific procedures.
- •Adults >=18 years at the time the ICF is signed.
- •History of one of the histologically documented hematologic malignancies according to the 5th edition of WHO classification as specified in the protocol.
- •NHL participants only: Agree to provide baseline tumor tissue samples as specified in the protocol.
- •ECOG PS of 0, 1 or 2 assessed no more than 14 days prior to initiation of trial intervention.
- •Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention as specified in the protocol.
- •Has an LVEF >=50% by either an ECHO or MUGA within 28 days before the trial starts.
- •Life expectancy of at least 3 months.
- •Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other trial procedures, and trial restrictions.
- •A woman of childbearing potential is eligible to participate if she meets all criteria as specified in the protocol.
- •A male participant capable of producing sperm is eligible to participate if he agrees to all criteria as specified in the protocol.
- •An individual who meets any of the following criteria will be excluded from participating in this trial:
- •Prior Allo-SCT.
- •Prior solid organ transplantation.
- •Inadequate washout period before initiation of trial intervention as specified in the protocol.
- •Evidence of brain or leptomeningeal disease (spinal cord or CNS metastases) based on history and physical examination, unless treated and with radiologically documented lack of progression within 4 weeks prior to initiation of trial intervention.
- •Uncontrolled or significant cardiovascular disease as specified in the protocol.
- •Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
- •Has a history of (noninfectious) ILD/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- •Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder and any autoimmune, connective tissue, or inflammatory disorder with potential pulmonary involvement, or prior pneumonectomy.
- •Has been diagnosed with another malignancy within the previous 3 years.
- •Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and lymphocytopenia) not yet resolved to NCI-CTCAE Version 5.0, Grade <=1 or baseline.
- •Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection.
- •Has active or uncontrolled HBV, HCV, or HIV infections.
排除标准
- 未提供
研究组 & 干预措施
Cohort A Combination Dose-escalation Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: Combination drug (Drug)
Monotherapy Dose Escalation Phase
Participants with hematological malignancies who received DS3790a monotherapy.
干预措施: DS3790a (Drug)
Monotherapy Dose Expansion Phase
Participants with hematological malignancies who received DS3790a monotherapy.
干预措施: DS3790a (Drug)
Cohort A Combination Dose-escalation Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: DS3790a (Drug)
Standard of Care
Participants with hematological malignancies who received standard of care (SoC).
干预措施: Combination drug (Drug)
Cohort B Randomization/Optimization Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: Combination drug (Drug)
Cohort A Randomization/Optimization Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: DS3790a (Drug)
Cohort A Phase 2
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: DS3790a (Drug)
Cohort A Randomization/Optimization Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: Combination drug (Drug)
Cohort A Phase 2
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: Combination drug (Drug)
Cohort B Combination Dose-escalation Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: DS3790a (Drug)
Cohort B Combination Dose-escalation Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: Combination drug (Drug)
Cohort B Randomization/Optimization Phase
Participants with hematological malignancies who received DS3790a monotherapy and selected combination regimen.
干预措施: DS3790a (Drug)
结局指标
主要结局
Number of Participants Reporting Dose-limiting Toxicities, Treatment-emergent Adverse Events, Serious Adverse Events, Adverse Events of Special Interest, and Deaths in Participants With Hematological Malignancies
时间窗: Baseline up to 5 years
Adverse events (AEs) will be graded using NCI-CTCAE version 5.0.
Complete Response in Participants With Hematological Malignancies by Blinded Independent Central Review (Cohort A Randomization Optimization Phase, Cohort A Phase 2)
时间窗: Baseline up to 5 years
Complete Response (CR) is defined as participants with CR as measured by BICR assessment.
Complete Response in Participants With Hematological Malignancies by Investigator Assessment (Cohort B Randomization Optimization Phase)
时间窗: Baseline up to 5 years
Complete Response (CR) is defined as participants with CR as measured by investigator assessment.
次要结局
- Complete Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Disease Control in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Duration of Complete Response and Duration of Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Time to Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Progression-free Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Overall Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Dose Expansion, and Cohorts A and B Dose Escalation)(Baseline up to 5 years)
- Objective Response by Investigator Assessment In Participants With Hematological Malignancies(Baseline up to 5 years)
- Complete Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)
- Disease Control in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)
- Duration of Complete Response and Duration of Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)
- Time to Response in Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)
- Progression-free Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)
- Overall Survival Participants With Hematological Malignancies by Investigator Assessment (Monotherapy Dose Escalation, Cohort A Combination Dose Escalation, Cohort B Combination Dose Escalation)(Baseline up to 5 years)