Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

Phase 2Active Not RecruitingNCT04663347

Genmab543 enrolled

Overview

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.

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

rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisoneDRUG

6 cycles (21-day cycles)

rituximab and lenalidomideDRUG

rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)

rituximab and bendamustineDRUG

6 cycles (28-day cycles)

rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatinDRUG

3 cycles (21-day cycles)

gemcitabine and oxaliplatinDRUG

4 cycles (28-day cycles)

EpcoritamabBIOLOGICAL

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.

rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisoneDRUG

6 cycles (21-day cycles)

LenalidomideDRUG

12 cycles (28-day cycles)

rituximab, ifosfamide, carboplatin, and etoposide phosphateDRUG

3 cycles (21-day cycles)

EpcoritamabBIOLOGICAL

Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.

EpcoritamabBIOLOGICAL

Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.

EpcoritamabBIOLOGICAL

Every week in cycle 1 and then every 8 weeks for a total of 2 years.

EpcoritamabBIOLOGICAL

Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.

EpcoritamabBIOLOGICAL

Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.

EpcoritamabBIOLOGICAL

Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.

EpcoritamabBIOLOGICAL

Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.

Rituximab and LenalidomideDRUG

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.

EpcoritamabBIOLOGICAL

Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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/Exclusion criteria may apply.

Locations (57)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Part 1: Number of Participants With Dose limiting Toxicities (DLTs)

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.

Time frame: During the first cycle (Cycle length= 28 days) in each cohort

Part 1 and Part 2 (Arms 1-5, 7 and 10): Number of Participants With Adverse Events (AEs)

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.

Time frame: 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)

Part 2 (Except Arm 7): Overall Response Rate (ORR)

ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.

Time frame: Up to 3 years