B-cell Non-Hodgkin Lymphoma B-cell Non-Hodgkin Lymphoma cancer
Conditions
Interventions
Epcoritamab (the investigational medicinal product [IMP]) will be administered
as a
subcutaneous injection. The schedules of administration are as follows:
Arm 1: epcoritamab + R-CHOP for 8 cycles (2
6 cycles of
epcoritamab in combination with SOC followed by 2 cycles of epcoritamab
monotherapy)
Arm 2: epcoritamab + rituximab + lenalidomide until progression (28-day cycles
12 cycles of epcoritamab in combination with SOC followed by epcoritamab
monotherapy until progression or unacceptable toxicity)
Arm 3: epcoritamab + BR for 8 cycles (21-day cycles
6 cycles in combination
with SOC followed by 2 cycles of epcoritamab monotherapy)
Arm 4: epcoritamab + R-DHAP until high-dose therapy with autologous stem cell
transplant (HDT-ASCT) (21-day cycles
3 cycles of epcoritamab in combination
with SOC followed by epcoritamab monotherapy until conditioning for transplant)
Arm 5: epcoritamab + GemOx until progression (28-day cycles
4 cycles in
combination with SOC followed by epcoritamab monotherapy until progression or
unacceptable toxicity)
Arm 6: epcoritamab + rituximab + lenalidomide, 12 cycles in combination
followed by
Sponsors
Genmab
Eligibility
Age
18 Years to 99 Years
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 representative (previous or current) 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 Arm 8, 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
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 cardiac 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 of 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 |
|---|---|
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| Dose Escalation Phase -PK parameters (clearance, volume of distribution, area under-the-concentration-time curve (AUC0-last and AUC0-*), 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 -Overall survival (OS) -Time to next anti-lymphoma therapy (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) -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 (ontreatment biopsy) -Incidence of ADAs to epcoritamab | — |
Countries
Netherlands
Outcome results
None listed