A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Genmab
- 入组人数
- 543
- 试验地点
- 77
- 主要终点
- Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating participants with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.
Trial details include:
- The treatment duration for each participant depends upon which arm of treatment they are assigned to.
- The visit frequency for each participant depends upon which arm of treatment they are assigned to, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
- All participants will receive active drug; no one will be given placebo.
Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.
Participants who receive standard treatments will have intravenous (IV) infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.
详细描述
A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL.
All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated:
- Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL)
- Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL)
- Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL
- Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
- Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
- Arm 6: epcoritamab + R2 in participants with previously untreated FL
- Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment
- Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
- Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy
- Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT
The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI). Applies to all arms except arm
- •Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
- •Acceptable organ function at screening
- •CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
- •If of childbearing potential participant must practicing a highly effective method of birth control
- •A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control
- •Newly diagnosed DLBCL
- •DLBCL, not otherwise specified (NOS)
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B
- •Arm 2: R/R FL
- •Arm 3: Newly diagnosed, previously untreated FL grade 1-3A
- •Documented R/R DLBCL and eligible for HDT-ASCT
- •DLBCL, NOS
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B
- •Documented R/R DLBCL and ineligible for HDT-ASCT
- •DLBCL, NOS
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B
- •Arm 6: Newly diagnosed, previously untreated FL grade 1-3A
- •FL Grade 1-3A
- •If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment.
- •Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
- •T-cell/histiocyte rich DLBCL
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B
- •Progressed within 24 months of initiating first-line treatment
- •Documented R/R DLBCL and eligible for HDT-ASCT
- •DLBCL, NOS
- •"Double-hit" or "triple-hit" DLBCL
- •FL Grade 3B
排除标准
- •Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
- •Any prior treatment with a bispecific antibody targeting CD3 and CD
- •Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
- •Clinically significant cardiovascular disease
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- •CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
- •Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- •Known history of seropositivity of human immunodeficiency virus (HIV)
- •Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
- •Neuropathy > grade 1
- •Receiving immunostimulatory agent
- •Prior allogeneic HSCT
- •Current seizure disorder requiring anti-epileptic therapy
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Arm 5 - Epcoritamab + GemOx
In participants with R/R DLBCL ineligible ASCT.
干预措施: Epcoritamab (Biological)
Arm 2 - Epcoritamab + R2
In participants with R/R FL.
干预措施: Rituximab and Lenalidomide (Drug)
Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL.
干预措施: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (Drug)
Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL.
干预措施: Epcoritamab (Biological)
Arm 2 - Epcoritamab + R2
In participants with R/R FL.
干预措施: Epcoritamab (Biological)
Arm 3 - Epcoritamab + BR
In participants with previously untreated FL.
干预措施: rituximab and bendamustine (Drug)
Arm 6 - Epcoritamab + R2
In participants with previously untreated FL.
干预措施: Epcoritamab (Biological)
Arm 7 - Epcoritamab maintenance
In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.
干预措施: Epcoritamab (Biological)
Arm 9 - Epcoritamab + Lenalidomide
In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.
干预措施: Epcoritamab (Biological)
Arm 8 - Epcoritamab + R mini-CHOP
In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.
干预措施: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone (Drug)
Arm 10 - Epcoritamab + R-ICE
In participants with R/R DLBCL eligible for ASCT.
干预措施: Epcoritamab (Biological)
Arm 6 - Epcoritamab + R2
In participants with previously untreated FL.
干预措施: rituximab and lenalidomide (Drug)
Arm 4 - Epcoritamab + R-DHAX/C
In participants with R/R DLBCL eligible for ASCT.
干预措施: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin (Drug)
Arm 5 - Epcoritamab + GemOx
In participants with R/R DLBCL ineligible ASCT.
干预措施: gemcitabine and oxaliplatin (Drug)
Arm 4 - Epcoritamab + R-DHAX/C
In participants with R/R DLBCL eligible for ASCT.
干预措施: Epcoritamab (Biological)
Arm 3 - Epcoritamab + BR
In participants with previously untreated FL.
干预措施: Epcoritamab (Biological)
Arm 8 - Epcoritamab + R mini-CHOP
In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.
干预措施: Epcoritamab (Biological)
Arm 10 - Epcoritamab + R-ICE
In participants with R/R DLBCL eligible for ASCT.
干预措施: rituximab, ifosfamide, carboplatin, and etoposide phosphate (Drug)
Arm 9 - Epcoritamab + Lenalidomide
In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
时间窗: During the first cycle (Cycle length= 28 days) in each cohort
DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
Part 1 and Part 2 (Arms 1-5, 7 and 10): Number of Participants With Adverse Events (AEs)
时间窗: From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Part 2 (Except Arm 7): Overall Response Rate (ORR)
时间窗: Up to 3 years
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
Part 1: Number of Participants With Dose limiting Toxicities (DLTs)
时间窗: During the first cycle (Cycle length= 28 days) in each cohort
DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.
Part 1 and Part 2 (Arms 1-5, 7 and 10): Number of Participants With Adverse Events (AEs)
时间窗: From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Part 2 (Except Arm 7): Overall Response Rate (ORR)
时间窗: Up to 3 years
ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.
次要结局
- Part 1 and 2: Number of Immune Cell Populations(Up to 2 years)
- Part 1 and 2: Percentage of Immune Cell Populations(Up to 2 years)
- Part 1 and 2: Duration of Complete Response (DoCR)(Up to 3 years)
- Part 1 and 2: Duration of Response (DOR)(Up to 3 years)
- Part 1 and 2: Time to Response (TTR)(Up to 3 years)
- Part 1 and 2: Progression Free Survival (PFS)(Up to 3 years)
- Part 1 and 2: Overall Survival (OS)(Up to 3 years)
- Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)(Up to 3 years)
- Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity(Up to 3 years)
- Part 1 and 2: Duration of minimal residual disease (MRD) negativity(Up to 3 years)
- Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity(Up to 3 years)
- Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10(Up to 3 years)
- Part 2 (Arm 7): Percentage of Participants With CR(Week 24, Week 48, and Week 96)
- Part 1 and 2: Time to Complete Response (TTCR)(Up to 3 years)
- Part 1 and 2: Clearance (CL) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Area Under the Concentration-Time Curve (AUC) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3(Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7))
- Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)(Up to 2 years)
- Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab(Up to 3 years)
- Part 1: ORR(Up to 3 years)
- Part 1 and 2: Clearance (CL) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Area Under the Concentration-Time Curve (AUC) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab(Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years))
- Part 1 and 2: Number of Immune Cell Populations(Up to 2 years)
- Part 1 and 2: Percentage of Immune Cell Populations(Up to 2 years)
- Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3(Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7))
- Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years)(Up to 2 years)
- Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab(Up to 3 years)
- Part 1: ORR(Up to 3 years)
- Part 1 and 2: Duration of Response (DOR)(Up to 3 years)
- Part 1 and 2: Time to Response (TTR)(Up to 3 years)
- Part 1 and 2: Progression Free Survival (PFS)(Up to 3 years)
- Part 1 and 2: Overall Survival (OS)(Up to 3 years)
- Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT)(Up to 3 years)
- Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity(Up to 3 years)
- Part 1 and 2: Duration of minimal residual disease (MRD) negativity(Up to 3 years)
- Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity(Up to 3 years)
- Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10(Up to 3 years)
- Part 2 (Arm 7): Percentage of Participants With CR(Week 24, Week 48, and Week 96)
- Part 1 and 2: Time to Complete Response (TTCR)(Up to 3 years)
- Part 1 and 2: Duration of Complete Response (DoCR)(Up to 3 years)
- Part 2: Number of Participants with AEs (Except Arm 7)(From first dose of drug until either 60 days after last dose, date participant withdraws consent, date participant starts a new systemic anticancer therapy, or date participant dies, whichever occurs first (up to approximately 3 years))