NCT03625037进行中（未招募）1 期
A Phase 1/2, Open-label Safety Trial of GEN3013 in Patients With Relapsed, Progressive or Refractory B-Cell Lymphoma
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 666
- 试验地点
- 152
- 主要终点
- Dose-Escalation: Dose Limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab, an antibody also known as EPKINLY™ and GEN3013 (DuoBody®-CD3xCD20):
- The dose schedule for epcoritamab
- The side effects seen with epcoritamab
- What the body does with epcoritamab once it is administered
- What epcoritamab does to the body once it is administered
- How well epcoritamab works against relapsed and/or refractory B-cell lymphoma
The trial consists of 3 parts:
- a dose-escalation part (Phase 1, first-in-human [FIH])
- an expansion part (Phase 2a)
- a dose-optimization part (OPT) (Phase 2a)
The trial time for each participant depends on which trial part the participant enters:
- For the dose-escalation part, each participant will be in the trial for approximately 1 year, which is made up of 21 days of screening, 6 months of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
- For the expansion and dose-OPT parts, each participant will be in the trial for approximately 1.5 years, which is made up of 21 days of screening, 1 year of treatment (the total time of treatment may be different for each participant), and 6 months of follow-up (the total time of follow-up may be different for each participant).
Participation in the study will require visits to the sites. During the first month, participants must visit every day or every few days, depending on which trial part the participant enters. After that, participants must visit weekly, every other week, once a month, and once every 2 months, as trial participation ends.
All participants will receive active drug, and no participants will be given placebo.
详细描述
The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase 2 dose (RP2D), as well as to establish the safety profile of epcoritamab in participants with relapsed or refractory B-cell lymphoma.
In the expansion part, additional participants will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab.
The dose-OPT part will evaluate alternative priming and intermediate dose regimens of epcoritamab in participants with:
- Diffuse large B-cell lymphoma (DLBCL)
- Follicular lymphoma (FL)
- Mantle cell lymphoma (MCL)
All participants will receive epcoritamab at the RP2D.
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
- •Main Inclusion Criteria - Escalation Part (recruitment completed)
- •Documented CD20+ mature B-cell neoplasm
- •DLBCL - de novo or transformed
- •MZL (nodal, extranodal or mucosa associated)
- •Relapsed and/or refractory disease following treatment with an anti-CD20 monoclonal antibody (e.g. rituximab) potentially in combination with chemotherapy and/or relapsed after autologous stem cell rescue.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or
- •Participants must have measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or Positron emission tomography-Computed tomography (PET-CT) scan
- •Acceptable renal function.
- •Acceptable liver function.
- •Main Inclusion Criteria - Expansion & Dose-OPT Parts
- •Documented CD20 positive mature B cell neoplasm or CD20+ MCL.
- •DLBCL, de novo or transformed (including double hit or triple hit).
- •FL grade 3B
- •Histologic confirmed FL
- •MCL (prior Bruton's tyrosine kinase inhibitor [BTKi] or intolerant to BTKi)
- •At least 2 therapies including an anti-CD20 monoclonal antibody containing chemotherapy combination regimen.
- •Either failed prior autologous hematopoietic stem cell transplantation (HSCT) or ineligible for autologous stem cell transplantation due to age or comorbidities.
- •At least 1 measurable site of disease based on CT, MRI or PET-CT scan with involvement of 2 or more clearly demarcated lesions and or nodes.
排除标准
- •All Parts
- •Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening.
- •Known past or current malignancy other than inclusion diagnosis.
- •Aspartate aminotransferase (AST), and/or alanine transaminase (ALT) >3 × upper limit of normal.
- •Total bilirubin >1.5 × upper limit of normal, unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin.
- •Estimated Creatinine clearance (CrCl) <45 milliliters (mL)/min.
- •Known clinically significant cardiovascular disease.
- •Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment). Past coronavirus disease 2019 (COVID-19) infection may be a risk factor.
- •Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
- •Seizure disorder requiring therapy (such as steroids or anti-epileptics).
- •Any prior therapy with an investigational bispecific antibody targeting CD3 and CD
- •Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days prior to first epcoritamab administration.
- •Eligible for curative intensive salvage therapy followed by high dose chemotherapy with HSCT rescue.
- •Autologous HSCT within 100 days prior to first epcoritamab administration, or any prior allogeneic HSCT or solid organ transplantation.
- •Active hepatitis B (deoxyribonucleic acid [DNA] polymerase chain reaction [PCR]-positive) or hepatitis C (ribonucleic acid [RNA] PCR-positive infection). Participants with evidence of prior hepatitis B (HBV) but who are PCR-negative are permitted in
- •Known human immunodeficiency virus (HIV) infection.
- •Exposed to live or live attenuated vaccine within 4 weeks prior to signing Informed consent form (ICF).
- •Pregnancy or breast feeding.
- •Participant is known or suspected of not being able to comply with the study protocol or has any condition for which, participation would not be in the best interest of the participant.
- •Contraindication to all uric acid lowering agents.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Epcoritamab
Experimental
Epcoritamab will be administered by subcutaneous injections in cycles of 28 days.
干预措施: Epcoritamab (Biological)
结局指标
主要结局
Dose-Escalation: Dose Limiting Toxicity (DLT)
时间窗: During the first cycle (28 days)
To determine the MTD and/or 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)
时间窗: From first dose until the end of the safety follow-up period (Up to 1 year)
An AE is any untoward medical occurrence in a clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.
Expansion: Overall Response Rate (ORR)
时间窗: Up to 1.5 years
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
Dose-OPT DLBCL, FL and MCL: Percentage of Participants with =>Grade 2 Cytokine Release Syndrome (CRS) Events and All Grade CRS Events
时间窗: From first dose until 7 days after second full dose (Day 28 for DLBCL; Day 35 for FL; Day 28-35 for MCL)
CRS will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
次要结局
- Expansion: Trough Concentration of Epcoritamab(Up to 1.5 years)
- Expansion and Dose-OPT MCL: CR Rate(Up to 1.5 years)
- Expansion and Dose-OPT MCL: DoCR(Up to 1.5 years)
- Dose-OPT DLBCL and FL: ORR(Up to 1.5 years)
- Dose-OPT DLBCL and FL: CR Rate(Up to 1.5 years)
- Dose-Escalation: Number of Participants with Anti-lymphoma Activity of Epcoritamab(Up to 1 year)
- Dose-Escalation: Duration of Response (DOR)(Up to 1 year)
- Expansion: DOR(Up to 1.5 years)
- Expansion Part: Changes in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym)(Up to 1.5 year)
- Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Following First Full Dose(Up to 1.5 years)
- Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Overall(Up to 1.5 years)
- Dose-OPT DLBCL and FL: Duration of CR (DoCR)(Up to 1.5 years)
- Dose-OPT DLBCL and FL: Progression-Free Survival (PFS)(Up to 1.5 years)
- Dose-OPT DLBCL and FL: DLT(During the first cycle (28 days) in each Dose-OPT Part (DLBCL, FL and MCL))
- Dose-OPT DLBCL, FL and MCL: DOR(Up to 1.5 years)
- Dose-Escalation and Dose-OPT DLBCL, FL and MCL: Pre-dose Values of Epcoritamab(Predose and postdose at multiple timepoints of each Cycle (Cycle length=28 days), up to approximately 1.5 years)
- Dose-Escalation, Expansion Part and Dose-OPT MCL: PFS(Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (MCL): 1.5 years)
- Expansion and Dose-OPT MCL: ORR(Up to 1.5 years)
- Expansion: Time to Response (TTR)(Up to 1.5 years)
- Expansion and Dose-OPT MCL: PFS(Up to 1.5 years)
- Expansion and Dose-OPT MCL: DOR(Up to 1.5 years)
- Expansion and Dose-OPT: TTR(Up to 1.5 years)
- Expansion and Dose-OPT DLBCL, FL and MCL: Number of Participants with AEs(Up to 7 years and 6 months)
- Expansion and Dose-OPT DLBCL, FL and MCL: Rate of Minimal Residual Disease (MRD) Negativity(Up to 1.5 years)
- All Parts: Number of Participants with CRS Events(Up to Day 1 of Cycle 12 (Cycle length=28 days))
- All Parts: Total Body Clearance of Epcoritamab from the Plasma (CL)(Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years)
- All Parts: Area under Curve (AUC) of Epcoritamab(Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years)
- All Parts: Maximum (peak) Plasma Concentration (Cmax) of Epcoritamab(Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years)
- All Parts: Time to Reach Cmax of Epcoritamab(Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years)
- All Parts: Half Life of Epcoritamab (t1/2)(Predose and postdose at multiple timepoints of each cycle (Cycle length=28 days), Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part: Up to 1.5 years)
- All Parts: Number of Participants with Anti-drug Antibody (ADA)(Up to 7 years and 6 months)
- All Parts: Time to Next Anti-lymphoma Therapy (TTNT)(Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part (DLBCL, FL and MCL): Up to 1.5 years)
- All Parts: Overall survival (OS)(Dose-Escalation: Up to 1 year; Expansion and Dose-OPT Part DLBCL, FL and MCL: Up to 1.5 years)
研究者
研究点 (152)
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相关资讯
Epcoritamab Approved by FDA for Relapsed/Refractory Follicular Lymphoma- The FDA has granted accelerated approval to epcoritamab for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.
- The approval was based on the phase 1/2 EPCORE NHL-1 trial, which demonstrated an 82% overall response rate and a 60% complete response rate.
- Epcoritamab addresses a significant unmet need in follicular lymphoma, offering a new option with higher response rates compared to existing therapies.
- As a bispecific antibody already approved for aggressive lymphomas, epcoritamab's integration into follicular lymphoma treatment is facilitated by existing familiarity among healthcare providers.last yearFDA Grants Accelerated Approval to Epcoritamab for Relapsed/Refractory Follicular Lymphoma- The FDA has granted accelerated approval to epcoritamab-bysp (Epkinly) for adult patients with relapsed/refractory follicular lymphoma (FL).
- This approval applies to patients who have previously undergone at least two lines of systemic therapy.
- The decision was based on data from the phase 1/2 EPCORE NHL-1 trial, which showed an overall response rate of 82%.
- The trial also demonstrated a complete response rate of 60% in patients treated with epcoritamab.2 years agoBispecific T-Cell Engagers Show Promise as Later-Line Therapies for Relapsed/Refractory DLBCL- Two bispecific T-cell engagers, epcoritamab-bysp and glofitamab-gxbm, received FDA accelerated approval in 2023 for relapsed/refractory diffuse large B-cell lymphoma, offering new treatment options for heavily pretreated patients.
- Both agents demonstrate remarkable activity with overall response rates above 50-60% and complete response rates around 40% in patients with CAR T-cell therapy failure, addressing a significant unmet medical need.
- Epcoritamab offers convenient subcutaneous administration in outpatient settings with manageable cytokine release syndrome rates below 3%, while glofitamab provides fixed-duration therapy with durable responses lasting over one year after treatment completion.
- These bispecific antibodies may challenge the paradigm that CAR T-cell therapy is the only curative option for relapsed/refractory patients, with emerging data suggesting potential for long-term disease control.3 years ago