B-Cell Non-Hodgkin Lymphoma
Conditions
Interventions
investigational material(s) Generic name etc : GEN3013 (DuoBody-CD3XCD20) INN of investigational material : epcoritamab Therapeutic category code : 429 Other antitumor agents Dosage and Administration
Sponsors
Genmab US Inc.
AbbVie
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main Inclusion Criteria: - Must be at least 20 years of age, inclusive - Japanese subjects - CD20 positivity at representative tumor biopsy a. Part 1: - Diffuse large B-cell lymphoma (de novo or histologically transformed) - High-grade B-cell lymphoma - Primary mediastinal large B-cell lymphoma - Follicular lymphoma - Marginal zone lymphoma (nodal, extranodal of mucosa-associated lymphoid tissue, or splenic) - Small lymphocytic lymphoma b. Part 2 : Arm 1: - Diffuse large B-cell lymphoma (de novo or histologically transformed) - Follicular lymphoma grade 1-3A - Relapsed or refractory disease and previously treated with at least 2 lines of systemic antineoplastic therapy including at least 1 anti-CD20 mAb-containing therapy. - Measurable disease by CT, MRI or PET-CT scan Arm 2: - R/R FL grade 1, 2 or 3a, stage II, III, or IV, without evidence of transformation. - Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody - Must have a need for treatment initiation based on symptoms and/ or disease burden (GELF criteria) - Eligible to receive R2 per investigator determination Arm 3: - One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) : o DLBCL, NOS o "Double-hit" or "triple-hit" DLBCL - FL Grade 3B. - T-cell/histiocyte rich LBCL - International Prognostic Index (IPI) score ?3 - No prior therapy for DLBCL or FL G3B other than nodal biopsy, corticosteroids, or palliative radiotherapy. - Eligible to receive R-CHOP per investigator determination Arm 4: - One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) including: o DLBCL, NOS. o "Double-hit" or "triple-hit" DLBCL o FL Grade 3B. o T-cell/histiocyte rich LBCL - Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody. - Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous HSCT - Eligible to receive GemOx per investigator determination Arm 5: - History of histologically confirmed CD20+ FL Grade 1-3a without evidence of transformation. - In CR or PR per Lugano criteria following first-line or second-line treatment with SOC regimen, including anti-CD20 antibody, and last dose of SOC within 6 months prior to enrollment
Exclusion criteria
Exclusion criteria: Main Exclusion Criteria: - Primary CNS lymphoma or CNS involvement by lymphoma at screening - Subjects not eligible for high dose therapy with autologous hematopoietic stem cell transplantation due to personal choice, social issues, or similar -Known clinically significant cardiac disease - Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment) Exclusion criteria for Part 2, Arms 2 through 5: Arm 2: - FL Grade 3b - Histologic evidence of transformation to an aggressive lymphoma - Contraindication to rituximab or lenalidomide - Unwilling or unable to take aspirin prophylaxis or prophylactic anticoagulant as clinically indicated Arm 3: - Contraindication to any of the individual drugs of the R-CHOP regimen Arm 4: - Contraindication to any of the individual drugs of the GemOx regimen Arm 5: - FL Grade 3b - Histologic evidence of transformation to an aggressive lymphoma
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy safety 1. Part 1: Incidence and severity of Adverse Events (AEs) Treatment emergent AEs. [Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose)] 2. Part 1: Incidence of Dose limiting toxicities (DLTs) To determine the RP2D and the MTD, if reached. [Time Frame: DLTs are assessed during the first cycle (28 days) in each cohort] 3. Part 2, Arm 1: Objective response rate (ORR) Antitumor activity as measured by the ORR according to Lugano classification [Time Frame: From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years] 4. Part 2, Arms 2-4: Incidence of DLTs [Time Frame: DLTs are assessed during the first cycle (28 days) in arms 2-4] 5. Part 2, Arms 2-5: Incidence and severity of AEs Treatment emergent AEs (TEAEs) [Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose)] | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy safety pharmacokinetics 6. Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 7. Both parts: AUC from Time 0 to Infinity (AUCinf) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 8. Both parts: Maximum (peak) plasma concentration (Cmax) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 9. Both parts: Time to reach Cmax (Tmax) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 10. Both parts: Pre-dose (trough) concentrations (Cthrough) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 11. Both parts: Total body clearance of drug from the plasma (CL) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 12. Both parts: Volume of distribution (Vd) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 13. Both parts: Elimination half-life (t 1/2) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 14. Both parts: Incidence of Anti-Drug-Antibodies (ADAs) [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 15. Part 1 and Part 2, Arm1: Number of participants with clinically significant shifts from baseline in clinical laboratory parameters Clinical laboratory parameters assessed: biochemistry, hematology [Time Frame: From first dose until treatment discontinuation, expected average of 1 year] 16. Part 2, Arm1: Incidence and severity of AEs TEAEs as assessed by CTCAE V5.0. [Time Frame: From first dose until the end of the safety follow-up period (60 days after last dose)] 17. Part 1 and Part 2, arms 2-5: ORR Defined as proportion of participants who have a PR or CR following treatment with epcoritamab. Determined by the Lugano resp | — |
Countries
Japan
Contacts
Public ContactYukiko Beppu
IQVIA Services Japan G.K.
Outcome results
None listed