Epcoritamab Combo for Non-Hodgkin's Lymphoma

Recruiting at 139 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Genmab

Must be taking: Anti-neoplastic agents

Must not be taking: Bispecific antibodies

Disqualifiers: Prior epcoritamab, unresolved toxicities, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

565 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for people with Non-Hodgkin's Lymphoma, a type of blood cancer. It evaluates the safety and tolerability of a drug called epcoritamab (a bispecific antibody) when combined with other cancer-fighting medications. The trial includes different groups, each testing unique drug combinations to determine the most effective for specific types of lymphoma. Individuals diagnosed with certain types of lymphoma and experiencing symptoms may be suitable candidates for this study. Participants will regularly visit a hospital or clinic for check-ups and treatment monitoring. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in lymphoma treatment.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that epcoritamab holds promise for treating certain types of Non-Hodgkin's Lymphoma. One study found that 73 patients with relapsed or hard-to-treat B-cell non-Hodgkin's lymphoma tolerated epcoritamab well, suggesting it might be safe, though further studies are needed for confirmation.

Lenalidomide and ibrutinib are generally well-tolerated in other treatments. Lenalidomide has proven effective when combined with epcoritamab in other studies. Ibrutinib is also undergoing trials with epcoritamab to assess their combined safety.

Polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone form a known treatment combination for certain lymphomas. These drugs are already used in other treatments, supporting their safety profile.

Pirtobrutinib and venetoclax are newer for this specific use but are being closely monitored in trials. They have been used in other cancer treatments and are considered safe with known side effects.

This trial is in an early phase, meaning treatments are still being tested for safety. Participants are monitored closely for any side effects. If a treatment is already approved for other conditions, it often indicates a level of safety. However, combining these drugs is still new, and data is being gathered to ensure safety in this specific use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about epcoritamab combos for treating non-Hodgkin's lymphoma because they offer a new approach compared to standard treatments like rituximab, chemotherapy, or BTK inhibitors. Epcoritamab is a bispecific antibody that targets both CD3 on T-cells and CD20 on B-cells, potentially enhancing the immune system's ability to attack cancer cells directly. This dual-targeting mechanism is different from traditional therapies that usually focus on one pathway, and it might lead to better outcomes for patients with relapsed or refractory lymphomas. Additionally, combining epcoritamab with other agents like ibrutinib or lenalidomide could maximize its effectiveness by attacking the cancer from multiple angles, providing new hope for those who have limited options.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma?

Research has shown that epcoritamab, one of the treatments in this trial, may help treat non-Hodgkin lymphoma (NHL) when combined with other cancer-fighting drugs. One study found that 64.3% of patients with relapsed or hard-to-treat diffuse large B-cell lymphoma responded to treatment, with 47.6% achieving a complete response. Another drug in this trial, CC-99282, has shown promising results and is considered safe for patients who have undergone many previous treatments for NHL. Ibrutinib, also part of this trial, has demonstrated a high response rate of 85% in some NHL types when used with other drugs. Venetoclax, combined with other treatments in this trial, has achieved a response rate of up to 87.5%, with many patients experiencing a complete response. Polatuzumab vedotin, another treatment option in this trial, has also improved complete response rates compared to standard treatments in NHL patients. These findings suggest that the various combinations of drugs, including epcoritamab, being tested in this trial may effectively treat various types of B-cell lymphomas. ^{6 7 8 9 10}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CC-99282
• Cyclophosphamide
• Doxorubicin Hydrochloride [HCl]
• Epcoritamab
• Ibrutinib
• Lenalidomide
• Polatuzumab Vedotin
• Prednisone
• Rituximab
• Venetoclax

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Epkinly for:

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Follicular lymphoma

Approved in European Union as Tepkinly for:

• Diffuse large B-cell lymphoma
• High-grade B-cell lymphoma
• Follicular lymphoma

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

Published Research Related to This Trial

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 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]

Epcoritamab, a bispecific antibody, showed strong efficacy in killing primary tumor cells from patients with newly diagnosed and relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), achieving median lysis rates of 65% to 84% across different lymphoma types.

The effectiveness of epcoritamab was consistent regardless of prior treatments, including CD20 monoclonal antibodies, indicating its potential as a treatment option for patients who have become resistant to existing therapies.

NCBI (Pubmed)

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. van der Horst, HJ., de Jonge, AV., Hiemstra, IH., et al.[2021]

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]

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]

Citations

1. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01538-5/fulltext

Results From CC-99282-NHL-001 (NCT03930953) a First- ... CC-99282 monotherapy demonstrated a manageable safety profile, with promising efficacy in heavily pretreated patients with R/R NHL.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2152265022015385

ABCL-412 Clinical Activity of CC-99282, a Novel, Oral ... CC-99282 monotherapy demonstrated a manageable safety profile, with promising efficacy in heavily pretreated patients with R/R NHL.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06209619

CC-99282 + Rituximab Early Post CART for Non-Hodgkin's ... Giving CC-99282 with rituximab may be a safe and effective treatment option for patients who have received CAR-T cell therapy for relapsed or refractory non- ...

4. onclive.com onclive.com/view/cc-99282-demonstrates-manageable-safety-profile-elicits-favorable-responses-in-non-hodgkin-lymphoma

CC-99282 Demonstrates Manageable Safety Profile, Elicits ... CC-99282 monotherapy displayed encouraging overall response rates (ORR) in patients with non-Hodgkin lymphoma (NHL), including B-cell lymphoma and follicular ...

5. mayo.edu mayo.edu/research/clinical-trials/cls-20552263

A Safety and Preliminary Efficacy Study of CC-99282, ... The purpose of this study is to evaluate the safety, tolerability, and preliminary effectiveness of CC-99282 alone and in combination with anti- ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04663347

NCT04663347 | Safety and Efficacy Trial of Epcoritamab ... The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...

7. nature.com nature.com/articles/s41375-024-02410-8

Epcoritamab in relapsed/refractory large B-cell lymphoma Findings in the present study of epcoritamab with median follow-up of 25.1 months were favorable, with median OS of 18.5 months. Further, to our ...

8. news.abbvie.com news.abbvie.com/2024-12-09-Two-Data-Analyses-From-Clinical-Trials-Show-Epcoritamab-DuoBody-R-CD3xCD20-Induces-Durable-Complete-Reponses-As-Monotherapy-and-Combination-Treatment-in-Patients-With-Diffuse-Large-B-Cell-Lymphoma

Two Data Analyses From Clinical Trials Show Epcoritamab ... DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) ... The safety and efficacy of epcoritamab have not been established for these ...

9. cancerresearch.org cancerresearch.org/blog/fda-approves-epkinly-for-relapsed-or-refractory-follicular-lymphoma

FDA approves EPKINLY® for relapsed or refractory ... This trial assessed the safety and initial efficacy of EPKINLY in 127 adult patients with relapsed or refractory follicular lymphoma (R/R FL).

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39708278/

Population Pharmacokinetics of Epcoritamab Following ... Epcoritamab is a medicine used to treat adults with certain forms of large B cell lymphoma after previous treatments have failed. Epcoritamab is a rationally ...