Epcoritamab Combo for Non-Hodgkin's Lymphoma

Recruiting at125 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Genmab

Must be taking: Anti-neoplastic agents

Must not be taking: Bispecific antibodies

Disqualifiers: Prior epcoritamab, unresolved toxicities, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new drug called epcoritamab, given with other cancer drugs, to treat adults with Non-Hodgkin lymphoma. The study aims to see if this combination is safe and effective. Participants will have periodic health evaluations to monitor their health and the treatment's impact.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves new drug combinations, it's best to discuss your current medications with the study doctors to ensure safety and compatibility.

Is epcoritamab safe for humans?

Epcoritamab has shown a manageable safety profile in patients with relapsed or refractory diffuse large B-cell lymphoma, with common side effects including cytokine release syndrome (CRS), injection-site reactions, and infections. CRS was mostly mild and resolved without leading to treatment discontinuation. ^{1 2 3 4 5}

What makes the Epcoritamab Combo drug unique for treating Non-Hodgkin's Lymphoma?

Epcoritamab is a novel drug that is administered subcutaneously (under the skin) and works by engaging T-cells to target and kill cancerous B-cells, which is different from many traditional treatments. It is a bispecific antibody, meaning it can bind to two different targets, CD3 and CD20, which helps direct the immune system to attack the lymphoma cells more effectively. ^{1 2 3 4 6}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

Adults with Non-Hodgkin lymphoma (NHL) including various subtypes like diffuse large B-cell lymphoma and mantle cell lymphoma. Participants must have a certain level of physical fitness, measurable disease sites, and no unresolved toxicities from previous cancer therapies above a mild grade, except for hair loss.

Inclusion Criteria

My condition is diagnosed as DLBCL, not otherwise specified.

I have been diagnosed with a specific type of lymphoma (DLBCL) that tests positive for CD20.

My condition is Grade 3B Follicular Lymphoma.

Exclusion Criteria

My side effects from previous cancer treatments are mild, except for hair loss.

I have not been treated with epcoritamab or similar drugs.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous epcoritamab in combination with various anti-neoplastic agents in 21, 28, or 56 day cycles depending on the treatment arm

Up to 5 years

Regular visits at approved institutions

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• CC-99282 (Protein Kinase Inhibitor)
• Cyclophosphamide (Chemotherapy)
• Doxorubicin Hydrochloride [HCl] (Topoisomerase II Inhibitor)
• Epcoritamab (Monoclonal Antibodies)
• Ibrutinib (BTK Inhibitor)
• Lenalidomide (Immunomodulatory Agent)
• Polatuzumab Vedotin (Monoclonal Antibodies)
• Prednisone (Corticosteroid)
• Rituximab (Monoclonal Antibodies)
• Venetoclax (BCL-2 Inhibitor)

Trial Overview The trial is testing the safety and effectiveness of Epcoritamab when combined with other anti-cancer drugs in treating NHL. Patients are grouped to receive different combinations based on their specific type of NHL, either as new patients or those who've relapsed after prior treatments.

Participant Groups

Group I: Arm 8: Dose Expansion Experimental Treatment 2 Interventions

Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.

Group II: Arm 8: Dose Escalation Experimental Treatment 2 Interventions

Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral pirtobrutinib in 28 day cycles in the first year and then 56 day cycles thereafter.

Group III: Arm 7: Dose Expansion Experimental Treatment 3 Interventions

Participants with newly diagnosed treatment-naïve MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Group IV: Arm 7: Dose Escalation Experimental Treatment 3 Interventions

Participants with newly diagnosed treatment-naïve MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Group V: Arm 6B: Dose Escalation Experimental Treatment 3 Interventions

Participants with R/R MCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib, and oral venetoclax in 28 day cycles.

Group VI: Arm 6A: Dose Escalation Experimental Treatment 2 Interventions

Participants with R/R mantle cell lymphoma (MCL) will receive escalating doses of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.

Group VII: Arm 6: Dose Expansion Experimental Treatment 2 Interventions

Participants with R/R MCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib in 28 day cycles.

Group VIII: Arm 5: Dose Expansion Experimental Treatment 2 Interventions

Participants with R/R FL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Group IX: Arm 5: Dose Escalation Experimental Treatment 2 Interventions

Participants with R/R follicular lymphoma (FL) will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Group X: Arm 4: Dose Expansion Experimental Treatment 2 Interventions

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Group XI: Arm 4: Dose Escalation Experimental Treatment 2 Interventions

Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral CC-99282 in 28 day cycles.

Group XII: Arm 3: Dose Expansion Experimental Treatment 6 Interventions

Participants newly diagnosed treatment-naïve DLBCL will receive the recommended dose of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.

Group XIII: Arm 3: Dose Escalation Experimental Treatment 6 Interventions

Participants with newly diagnosed treatment-naïve DLBCL will receive escalating doses of SC epcoritamab in combination with intravenous (IV) polatuzumab vedotin, IV rituximab, IV cyclophosphamide, IV doxorubicin hydrochloride (HCl), and oral prednisone (pola-R-CHP) in 21 day cycles.

Group XIV: Arm 2: Dose Expansion Experimental Treatment 3 Interventions

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.

Group XV: Arm 2: Dose Escalation Experimental Treatment 3 Interventions

Participants with R/R DLBCL will receive escalating doses of SC epcoritamab in combination with oral ibrutinib and oral lenalidomide in 28 day cycles.

Group XVI: Arm 1: Dose Expansion Experimental Treatment 2 Interventions

Participants with R/R DLBCL will receive the recommended dose of SC epcoritamab in combination with oral lenalidomide in 28 day cycles.

Group XVII: Arm 1: Dose Escalation Experimental Treatment 2 Interventions

Participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) will receive escalating doses of subcutaneous (SC) epcoritamab in combination with oral lenalidomide in 28 day cycles.

CC-99282 is already approved in Canada for the following indications:

Approved in Canada as Epkinly/Tepkinly for:

• Diffuse large B-cell 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

Epcoritamab, a bispecific antibody targeting CD3 and CD20, was found to be safe and well-tolerated in 73 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, with no dose-limiting toxic effects and a recommended phase 2 dose established at 48 mg.

The treatment showed promising efficacy, with an overall response rate of 68% in patients with diffuse large B-cell lymphoma and 90% in those with follicular lymphoma, indicating its potential as a viable therapy for these difficult-to-treat conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Hutchings, M., Mous, R., Clausen, MR., et al.[2021]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, showed a 63.1% overall response rate in 157 patients with relapsed or refractory large B-cell lymphoma, indicating its efficacy in this challenging patient population.

The treatment was generally well-tolerated, with manageable side effects; however, cytokine release syndrome was common (49.7%), and there was one reported fatality due to immune effector cell-associated neurotoxicity syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. Thieblemont, C., Phillips, T., Ghesquieres, H., et al.[2023]

Epcoritamab is a bispecific antibody that targets CD3 and CD20, designed for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and received conditional approval in the USA on May 19, 2023, for adult patients after at least two prior therapies.

The drug has also received a positive opinion in the EU and is under review in Japan, indicating its potential as a significant treatment option for patients with difficult-to-treat B-cell non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epcoritamab: First Approval. Frampton, JE.[2023]

Epcoritamab, a bispecific antibody targeting CD3 and CD20, demonstrated a 55.6% overall response rate and a 44.4% complete response rate in 36 Japanese patients with relapsed or refractory CD20+ B-cell non-Hodgkin's lymphoma after a median follow-up of 8.4 months.

The treatment had a manageable safety profile, with cytokine release syndrome being the most common adverse event (83.3%), primarily low grade, and all cases resolved without leading to treatment discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. Izutsu, K., Kumode, T., Yuda, J., et al.[2023]

In the phase III CLL14 trial, a 12-month treatment with venetoclax combined with obinutuzumab significantly improved progression-free survival and rates of undetectable minimal residual disease compared to traditional chemoimmunotherapy with chlorambucil and obinutuzumab in patients with untreated chronic lymphocytic leukaemia.

Venetoclax + obinutuzumab is a well-tolerated, chemotherapy-free treatment option for CLL, with manageable side effects like neutropenia, making it suitable for patients who cannot undergo intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. Blair, HA.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. [2021]

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

Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. [2023]

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

Epcoritamab: First Approval. [2023]

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

Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma. [2023]

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

Venetoclax: A Review in Previously Untreated Chronic Lymphocytic Leukaemia. [2021]

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

Epcoritamab induces potent anti-tumor activity against malignant B-cells from patients with DLBCL, FL and MCL, irrespective of prior CD20 monoclonal antibody treatment. [2021]