Epcoritamab Combinations for Non-Hodgkin's Lymphoma

(EPCORE™ NHL-2 Trial)

Recruiting at 62 trial locations

Overseen By Genmab A/S Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genmab

Must not be taking: Immunostimulatory agents

Disqualifiers: Cardiovascular disease, CNS lymphoma, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

543 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy, radiation therapy, or major surgery within 4 weeks before starting the trial, and certain other treatments like CAR-T therapy are also restricted.

What data supports the effectiveness of the drug combination including Epcoritamab for treating non-Hodgkin's lymphoma?

Research shows that bendamustine, when combined with other drugs like rituximab, has been effective in treating non-Hodgkin's lymphoma, with high response rates in patients whose disease was difficult to treat. This suggests that combining bendamustine with other drugs, like Epcoritamab, could also be effective. ^{1 2 3 4 5}

Is Epcoritamab and its combinations safe for treating Non-Hodgkin's Lymphoma?

Bendamustine, a drug often used in combination with others for treating lymphoma, has been studied for safety. In trials, it showed some side effects like mucositis (mouth sores), gastroenteritis (stomach issues), and skin reactions, but serious side effects were less common. Overall, it was considered safe when used in specific doses, but patients with pre-existing kidney issues should be cautious. ^{4 6 7 8 9}

What makes the Epcoritamab combination treatment unique for Non-Hodgkin's Lymphoma?

The Epcoritamab combination treatment is unique because it includes a novel drug, Epcoritamab, which is a bispecific antibody designed to engage the immune system to target and destroy cancer cells. This approach is different from traditional chemotherapy regimens, which primarily focus on directly killing cancer cells, and it may offer a new option for patients with Non-Hodgkin's Lymphoma. ^{2 3 10 11 12}

Eligibility Criteria

This trial is for adults with B-cell Non-Hodgkin Lymphoma who are in relatively good health (ECOG PS score of 0-2), have measurable disease, and proper organ function. They must not have had certain treatments like bispecific antibodies or CAR-T therapy recently, no active infections like TB or hepatitis, and no history of HIV. Participants should use effective birth control.

Inclusion Criteria

My lymphoma is CD20-positive.

I am a man willing to use contraception if my partner can have children.

If of childbearing potential subject must practicing a highly effective method of birth control

Exclusion Criteria

My neuropathy is mild or I don't have it.

I am on medication for my seizure disorder.

I have had a stem cell transplant from a donor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive varying doses of epcoritamab to assess safety and determine the most appropriate dose

28 days

Weekly visits

Dose Expansion

Participants receive the selected dose of epcoritamab to assess preliminary efficacy

Up to 3 years

Visits every 2 to 8 weeks depending on treatment arm

Follow-up

Participants are monitored for safety and effectiveness after treatment

60 days after last dose

Treatment Details

Interventions

• Bendamustine
• Carboplatin
• Cisplatin
• Cyclophosphamide
• Cytarabine
• Dexamethasone
• Doxorubicin
• Epcoritamab
• Gemcitabine
• Oxaliplatin
• Prednisone
• Rituximab
• Vincristine

Trial Overview The trial tests Epcoritamab combined with standard cancer drugs in people with B-NHL. It's an early-stage multinational study to check the safety, how the body processes it, immune response, and initial effectiveness against lymphoma.

Participant Groups

Group I: Arm 9 - Epcoritamab + Lenalidomide Experimental Treatment 2 Interventions

In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.

Group II: Arm 8 - Epcoritamab + R mini-CHOP Experimental Treatment 2 Interventions

In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.

Group III: Arm 7 - Epcoritamab maintenance Experimental Treatment 1 Intervention

In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.

Group IV: Arm 6 - Epcoritamab + R2 Experimental Treatment 2 Interventions

In participants with previously untreated FL.

Group V: Arm 5 - Epcoritamab + GemOx Experimental Treatment 2 Interventions

In participants with R/R DLBCL ineligible ASCT.

Group VI: Arm 4 - Epcoritamab + R-DHAX/C Experimental Treatment 2 Interventions

In participants with R/R DLBCL eligible for ASCT.

Group VII: Arm 3 - Epcoritamab + BR Experimental Treatment 2 Interventions

In participants with previously untreated FL.

Group VIII: Arm 2 - Epcoritamab + R2 Experimental Treatment 3 Interventions

In participants with R/R FL.

Group IX: Arm 10 - Epcoritamab + R-ICE Experimental Treatment 2 Interventions

In participants with R/R DLBCL eligible for ASCT.

Group X: Arm 1 - Epcoritamab + R-CHOP Experimental Treatment 2 Interventions

In participants with previously untreated DLBCL.

Bendamustine is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

Bendamustine has been approved for treating chronic lymphocytic leukemia and has shown good response rates with minor side effects when used alone for non-Hodgkin's lymphomas.

When combined with rituximab and other agents, bendamustine significantly improves efficacy, making it a valuable option for treating relapsed indolent non-Hodgkin's lymphomas, with less toxicity compared to traditional R-CHOP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in the treatment of non-Hodgkin's lymphomas. Hagemeister, F., Manoukian, G.[2021]

The combination of bendamustine and rituximab showed promising therapeutic efficacy in treating lymphoproliferative diseases, achieving an overall response rate of 65% in chronic lymphocytic leukemia (CLL) and 96% in indolent lymphoma among 71 patients studied.

However, the treatment was associated with significant hematotoxicity, with severe neutropenia and thrombocytopenia occurring in 33% and 18% of patients, respectively, and a notable risk of severe infections in aggressive lymphoma and CLL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. Waldthaler, C., Stauder, R., Schnallinger, M., et al.[2021]

In a study involving 73 patients with relapsed or refractory follicular lymphoma, the combination of bortezomib, bendamustine, and rituximab achieved an impressive overall response rate of 88%, with 53% of patients experiencing a complete response.

The treatment demonstrated a median progression-free survival of 14.9 months, and while there were manageable toxicities, including myelosuppression, the overall safety profile was acceptable for patients undergoing this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. Fowler, N., Kahl, BS., Lee, P., et al.[2020]

The T(R)EC regimen, which replaces ifosfamide with bendamustine, demonstrated high response rates of 85% in classic Hodgkin lymphoma and 65% in diffuse large B cell lymphoma, indicating its efficacy as a treatment for relapsed or refractory cases.

This outpatient treatment was found to be safe, with no dose-limiting toxicities and successful stem cell collection in 30 out of 32 patients, making it a promising alternative to the traditional (R)ICE regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. Budde, LE., Wu, D., Martin, DB., et al.[2022]

Bendamustine demonstrated a high objective response rate of 74.3% in 99 patients with relapsed/refractory Hodgkin and non-Hodgkin lymphoma, indicating its efficacy as a salvage treatment after multiple lines of chemotherapy.

The most common side effects included lymphopenia, anemia, and neutropenia, with serious side effects occurring in a minority of patients, suggesting that while bendamustine is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. Karadurmus, N., Paydas, S., Esin, E., et al.[2022]

Bendamustine hydrochloride is a newer alkylating agent that has shown promise in treating resistant or refractory cancers due to its unique pharmacological properties.

The article reviews clinical trials demonstrating bendamustine's effectiveness both as a standalone treatment and in combination therapies for various solid tumors and blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine hydrochloride - a renaissance of alkylating strategies in anticancer medicine. Eichbaum, M., Bischofs, E., Nehls, K., et al.[2017]

Bendamustine used as a conditioning regimen for autologous stem cell transplantation in 35 lymphoma patients resulted in successful hematopoietic reconstitution, with median times of 11 days for neutrophil and 12 days for platelet engraftment, and a high overall survival rate of 90.97% at 12 and 24 months.

The treatment was associated with manageable side effects, including nausea, vomiting, and diarrhea, with no transplant-related deaths reported, indicating that bendamustine is both effective and tolerable for patients undergoing this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma]. Fu, Y., Feng, YF., Liu, F., et al.[2023]

Salvage chemotherapy followed by high-dose therapy and autologous stem cell transplantation is the standard treatment for relapsed diffuse large B-cell lymphoma, but the addition of rituximab has improved outcomes after first-line treatment and relapses.

The CORAL trial found no significant difference in response rates between two salvage regimens (R-ICE and R-DHAP), and identified that factors like early relapse and certain genetic markers significantly affect survival, indicating that over 70% of patients may not benefit from standard salvage therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? Gisselbrecht, C.[2022]

In a study of 22 patients with resistant and relapsed CD20-positive follicular non-Hodgkin's lymphoma, the combination treatment of rituximab, high-dose cytarabine, oxaliplatin, and dexamethasone (R-DHAOx) resulted in a remarkable 95% complete response rate, demonstrating its efficacy as a salvage therapy.

With a median follow-up of 58.3 months, the treatment showed long-term effectiveness, with an 84% progression-free survival rate at 38.2 months, although it was associated with significant side effects like peripheral neuropathy and myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma. Machover, D., Delmas-Marsalet, B., Misra, SC., et al.[2015]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Bendamustine in the treatment of non-Hodgkin's lymphomas. [2021]

2. Austria pubmed.ncbi.nlm.nih.gov

Routine use of bendamustine and rituximab combination therapy in consecutive patients with lymphoproliferative diseases: a survey from Tyrolean hospitals. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Bendamustine with rituximab, etoposide and carboplatin (T(R)EC) in relapsed or refractory aggressive lymphoma: a prospective multicentre phase 1/2 clinical trial. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Bendamustine, vincristine, prednisolone (BOP) in therapy of advanced low-grade non-Hodgkin lymphoma]]. [2015]

6. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]

7. Spain pubmed.ncbi.nlm.nih.gov

Bendamustine hydrochloride - a renaissance of alkylating strategies in anticancer medicine. [2017]

8. China pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma]. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Bendamustine-based conditioning prior to autologous stem cell transplantation (ASCT): Results of a French multicenter study of 474 patients from LYmphoma Study Association (LYSA) centers. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Is there any role for transplantation in the rituximab era for diffuse large B-cell lymphoma? [2022]

11. France pubmed.ncbi.nlm.nih.gov

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma. [2015]

12. England pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. [2022]