Diffuse Large B-Cell Lymphoma, Follicular Lymphoma
Conditions
Keywords
DuoBody®, monoclonal antibodies, anti-CD3, anti-CD20
Brief summary
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.
Detailed description
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.
Interventions
6 cycles (21-day cycles)
rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)
6 cycles (28-day cycles)
DRUGrituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
3 cycles (21-day cycles)
4 cycles (28-day cycles)
BIOLOGICALEpcoritamab
Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
DRUGrituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
6 cycles (21-day cycles)
DRUGLenalidomide
12 cycles (28-day cycles)
DRUGrituximab, ifosfamide, carboplatin, and etoposide phosphate
3 cycles (21-day cycles)
Rituximab 375 milligrams per meter squared (mg/m\^2) will be administered intravenously QW in Cycle 1 and Q4W in Cycles 2-5. Lenalidomide 20 mg will be administered orally daily for 21 days for 12 cycles.
Sponsors
Genmab
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria 1. 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 7. 2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2 3. Acceptable organ function at screening 4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy 5. If of childbearing potential participant must practicing a highly effective method of birth control 6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1: * 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 Arm 4: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Arm 5: * 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 Arm 7: * 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. Arm 8: * 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 Arm 9: * R/R FL * Progressed within 24 months of initiating first-line treatment Arm 10: * Documented R/R DLBCL and eligible for HDT-ASCT * DLBCL, NOS * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B Key
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. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic 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. Neuropathy \> grade 1 11. Receiving immunostimulatory agent 12. Prior allogeneic HSCT 13. Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2 (Except Arm 7): Overall Response Rate (ORR) | 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) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | It is defined as the percentage of participants who remain in complete remission or converting to complete remission after first trial drug administration. |
| Part 1 and 2: Time to Complete Response (TTCR) | Up to 3 years | TTCR is defined as the time from first trial drug administration to the date of first documented complete response post-treatment. |
| Part 1 and 2: Duration of Complete Response (DoCR) | Up to 3 years | DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs first based on Lugano criteria. |
| 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) | 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 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 | Immune cell populations in peripheral blood and tumor biopsies will be assessed. |
| Part 1 and 2: Percentage of Immune Cell Populations | Up to 2 years | Immune cell populations in peripheral blood and tumor biopsies will be assessed. |
| 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) | Change in cytokine levels in peripheral blood samples will be assessed. |
| 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 | Change in circulating tumor DNA levels will be assessed. |
| 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 | ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria. |
| Part 1 and 2: Duration of Response (DOR) | Up to 3 years | DOR: the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death, whichever occurs earlier, based on Lugano criteria. |
| Part 1 and 2: Time to Response (TTR) | Up to 3 years | TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (CR or PR). |
| Part 1 and 2: Overall Survival (OS) | Up to 3 years | OS is defined as the time from the date of first dose, to the date of death due to any cause. |
| Part 1 and 2: Progression Free Survival (PFS) | Up to 3 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. |
| Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT) | Up to 3 years | TTNT is defined as the time from Day 1 of Cycle 1 to first documented administration of subsequent anti-lymphoma therapy. |
| Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity | Up to 3 years | It is defined as the percentage of participants with at least 1 MRD negative result. |
Countries
Australia, Belgium, Czechia, Denmark, Finland, France, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom, United States
Outcome results
None listed