B-cell Non-Hodgkin Lymphoma Diffuse large B-cell lymphoma Non-Hodgkin lymphoma Follicular lymphoma MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Epcoritamab
Product Code: GEN3013
Pharmaceutical Form: Concentrate and solvent for solution for injection
INN or Proposed INN: epcoritamab
CAS Number: 2134641-34-0
Other descriptive name
Sponsors
Genmab A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject must sign an ICF 2. At least 18 years of age 3. 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 CT or MRI 4. ECOG PS score of 0, 1 or 2 5. Acceptable organ function at screening 6. CD20-positive NHL at most recent representative tumor biopsy 7. If of childbearing potential subject must practicing a highly effective method of birth control 8. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control 9. Life expectancy >2 months with SOC treatment. Arm 1: One of these confirmed histologies: - DLBCL, NOS - T-cell/histiocyte rich DLBCL - "double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 2 and Arm 9: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4 and Arm 10: One of these confirmed histologies and eligible for HDT-ASCT - DLBCL, NOS - T-cell/histiocyte rich DLBCL - "double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 5: One of these confirmed histologies and ineligible for HDT-ASCT - DLBCL, NOS - T-cell/histiocyte rich DLBCL - "double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 6: previously untreated CD20+ FL Arm 7: FL and in CR or PR per Lugano criteria following first-line or second-line treatment with SOC regiment and last dose of SOC within 6 months prior to enrollment Arm 8: One of these confirmed histologies: - DLBCL, NOS - T-cell/histiocyte rich DLBCL - "double-hit" or "triple-hit" DLBCL -FL Grade 3B For Arm8, subjects must be ineligible to receive full-dose anthracycline (as part of R-CHOP) per eligibility criteria Arm 9: Must have received only 1 prior line of therapy. This first-line therapy must have included an anti-CD20 antibody in combination with chemotherapy. Progressed within 24 months of initiating first-line treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 331 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 331
Exclusion criteria
Exclusion criteria: 1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab 2. Any prior treatment with a bispecific antibody targeting CD3 and CD20. 3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab 4. Clinically significant cardiovascular disease 5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results 6. 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 7. Active HBV or HBC (DNA PCR positive infection) 8. Known history of seropositivity for human immunodeficiency virus (HIV) 9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months 10. Subject has current seizure disorder requiring anti-epileptic therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose Escalation Phase: Evaluate the safety and tolerability of epcoritamab in combination with other agents Expansion Phase: Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents Expansion Phase: Arms 1-6 and 8-10: Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents Arm 7: Evaluate the safety and tolerability of epcoritamab following standard of care (SOC) ;Secondary Objective: Dose Escalation Phase: - Characterize the pharmacokinetic (PK) properties of epcoritamab - Evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab - Evaluate immunogenicity - Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents Expansion Phase: - Further assess the preliminary anti-tumor activity of epcoritamab in combination with other agents - Further evaluate the safety and tolerability of epcoritamab in combination with other agents - Characterize the PK properties of epcoritamab - To evaluate pharmacodynamic markers linked to efficacy and mechanism of action of epcoritamab - Evaluate immunogenicity ;Primary end point(s): Dose Escalation Phase: - Incidence of dose-limiting toxicities - Incidence and severity of adverse events (AEs) - Incidence and severity of changes in laboratory values - Incidence of dose interruptions and delays Expansion Phase: Arms 1-6 and 8-10: - ORR determined by Lugano criteria Arm 7: - Incidence and severity of AEs - Incidence and severity of changes in laboratory values - Incidence of dose interruptions and delays ;Timepoint(s) of evaluation of this end point: DLT evaluation period is defined as the first 4 weeks, ie, 28 days after the first administration of epcoritamab. For the other end points, please refer to protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Dose Escalation Phase: - PK parameters (clearance, volume of distribution, area under-the-concentration-time curve [AUC0-last and AUC0-8], maximum concentration [Cmax], time of Cmax [Tmax], predose values, and half-life) - Pharmacodynamic markers in blood samples and within tumor (on-treatment biopsy) - Incidence of anti-drug antibodies (ADAs) to epcoritamab - ORR determined by Lugano criteria - Duration of response (DOR) determined by Lugano criteria - Time to response (TTR) determined by Lugano criteria - Progression-free survival (PFS) determined by Lugano criteria - ORR determined by Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) - DOR determined by LYRIC - TTR determined by LYRIC - PFS determined by LYRIC - Overall survival (OS) - TTNT - Rate and duration of minimal residual disease (MRD) negativity Expansion Phase: -DOR determined by Lugano criteria (Arms 1-6 and 8-10) -TTR determined by Lugano criteria (Arms 1-6 and 8-10) -PFS determined by Lugano criteria (Arms 1-6 and 8-10) -ORR determined by LYRC LYRIC (Arms 1-6 and 8) -DOR determined by LYRIC (Arms 1-6 and 8) -TTR determined by LYRIC (Arms 1-6 and 8) -PFS determined by LYRIC (Arms 1-6 and 8) -CR rate (Arm 1-10 except Arm 7 subjects in CR at baseline) -OS (Arms 1-10) -TTNT (Arms 1-10) -Rate and duration of MRD negativity (Arms 1-10) -Rate of conversion from MRD positivity to MRD negativity (Arm 7) -CR rate (Arm 7 subjects in PR at baseline) -TTCR (Arms 1-10, except Arm 7 subjects in CR at baseline) -DoCR (Arms 1-10) -Incidence and severity of AEs (Arms 1-6, and 8-10) -Incidence and severity of changes in laboratory values (Arms 1-6, and 8-10) -Incidence of dose interruptions and delays (Arms 1-6, and 8-10) -PK parameters -Pharmacodynamic markers in blood samples and within tumor (on-treatment biopsy) -Incidence of ADAs to epcoritamab;Timepoint(s) of evaluation of this end point: Please refer to protocol | — |
Countries
Australia, Belgium, Canada, Czechia, Czech Republic, Denmark, Finland, France, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Genmab A/S
Outcome results
None listed