Aggressive B-cell Non-Hodgkin Lymphoma (aNHL), DLBCL, FL, High-grade B-cell Lymphoma (HGBCL), Indolent B-cell Non-Hodgkin Lymphoma (iNHL), Marginal Zone Lymphoma (MZL), MCL, Primary Mediastinal Large B-cell Lymphoma (PMBCL), Small Lymphocytic Lymphoma (SLL)
Conditions
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALEpcoritamab
Administered as specified in the treatment arm.
Sponsors
Genmab
AbbVie
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria - Escalation Part (recruitment completed) * Documented CD20+ mature B-cell neoplasm 1. DLBCL - de novo or transformed 2. HGBCL 3. PMBCL 4. FL 5. MCL 6. SLL 7. 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 2. * 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). * PMBCL * FL grade 3B * Histologic confirmed FL * MZL * SLL * 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. Main
Exclusion criteria
- 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 CD20. * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose-Escalation: Dose Limiting Toxicity (DLT) | 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) | 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) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expansion and Dose-OPT MCL: ORR | Up to 1.5 years | ORR is defined as the percentage of participants achieving CR or PR based on LYRIC. |
| Expansion: Time to Response (TTR) | Up to 1.5 years | TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on Lugano criteria. |
| Expansion and Dose-OPT MCL: PFS | Up to 1.5 years | PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on LYRIC. |
| Expansion and Dose-OPT MCL: DOR | Up to 1.5 years | DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on LYRIC. |
| Expansion and Dose-OPT: TTR | Up to 1.5 years | TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (PR or better) earlier based on LYRIC. |
| Dose-OPT DLBCL and FL: Duration of CR (DoCR) | Up to 1.5 years | DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier assessed by investigator. |
| Dose-OPT DLBCL and FL: Progression-Free Survival (PFS) | Up to 1.5 years | PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier assessed by investigator. |
| Dose-OPT DLBCL and FL: DLT | During the first cycle (28 days) in each Dose-OPT Part (DLBCL, FL and MCL) | To determine the MTD and/or RP2D to be studied in the expansion part. DLT will be graded according to NCI-CTCAE version 5.0. |
| Dose-OPT DLBCL, FL and MCL: DOR | Up to 1.5 years | DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria assessed by investigator. |
| Dose-Escalation: Number of Participants with Anti-lymphoma Activity of Epcoritamab | Up to 1 year | Anti-lymphoma activity will be evaluated as number of participants with resolution of constitutional symptoms, reduction in tumor size, objective, and best response (ORR, CR and PR). |
| Dose-Escalation: Duration of Response (DOR) | Up to 1 year | DOR is defined as the time from the first documentation of response (CR or PR) to the date of progressive disease (PD) or death, whichever occurs earlier as assessed by the investigator. |
| Expansion: DOR | Up to 1.5 years | DOR is defined as the time from the first documentation of response (CR or PR) to the date of PD or death, whichever occurs earlier based on Lugano criteria. |
| Expansion Part: Changes in Lymphoma Symptoms as Measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | Up to 1.5 year | Change from baseline in health-related quality of life over time and in relation to treatment will be evaluated using FACT-Lym scale. |
| 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 | CRS will be graded based on ASTCT criteria. |
| Dose-OPT DLBCL and FL: Percentage of Participants with >=Grade 2 CRS Events and All Grade CRS Events Overall | Up to 1.5 years | CRS will be graded based on ASTCT criteria. |
| Dose-OPT DLBCL and FL: ORR | Up to 1.5 years | ORR is defined as the percentage of participants achieving CR or PR assessed by investigator. |
| Dose-OPT DLBCL and FL: CR Rate | Up to 1.5 years | CR rate is defined as the percentage of participants with CR assessed by investigator. |
| Expansion and Dose-OPT DLBCL, FL and MCL: Number of Participants with AEs | Up to 7 years and 6 months | 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 and Dose-OPT DLBCL, FL and MCL: Rate of Minimal Residual Disease (MRD) Negativity | Up to 1.5 years | MRD is defined as percentage of participants with at least 1 MRD negative result. |
| All Parts: Number of Participants with CRS Events | Up to Day 1 of Cycle 12 (Cycle length=28 days) | CRS will be graded based on ASTCT criteria. |
| 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 | Plasma samples will be screened for antibodies binding to epcoritamab, and for confirmed positive samples, the titer against the two specific arms of epcoritamab will be reported. |
| 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 | TTNT is defined as the time from Day 1 of Cycle 1 to first recorded administration of subsequent anti-lymphoma therapy or death due to any cause, whichever occurs earlier. |
| 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 | OS is defined as the time from Day 1 of Cycle 1 to death. |
| 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 | — |
| Expansion: Trough Concentration of Epcoritamab | Up to 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 | PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause, whichever occurs earlier based on Lugano criteria. |
| Expansion and Dose-OPT MCL: CR Rate | Up to 1.5 years | CR rate is defined as the percentage of participants with CR based on Lugano criteria. |
| Expansion and Dose-OPT MCL: DoCR | Up to 1.5 years | DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs earlier based on Lugano criteria. |
Countries
Australia, Canada, Denmark, Finland, France, Germany, Italy, Netherlands, Poland, Singapore, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Official
Genmab
Outcome results
None listed