Epcoritamab + Chemotherapy for Diffuse Large B-Cell Lymphoma

Overseen By Selina Laqui

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Must not be taking: Bispecific T-cell engagers

Disqualifiers: Active infections, CNS involvement, 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: 14

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well epcoritamab in combination with standard of care (SOC) platinum-based chemotherapy (rituximab, ifosfamide, carboplatin, etoposide \[RICE\], rituximab, cytarabine, dexamethasone, oxaliplatin or carboplatin RDHAP/X\] or gemcitabine and oxaliplatin \[Gem/Ox\]) and autologous hematopoietic cell transplant (HCT) works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab, a type of bispecific T-cell engager, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as ifosfamide, etoposide phosphate, cytarabine, and gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. An autologous HCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving epcoritamab in combination with SOC platinum-based chemotherapy, such as RICE, RDHAP/X and Gem/Ox, and autologous HCT may kill more cancer cells in patients with relapsed or refractory LBCL.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use other anti-cancer treatments or investigational drugs close to starting the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Epcoritamab for treating Diffuse Large B-Cell Lymphoma?

Epcoritamab has shown strong anti-tumor activity in patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL), with studies reporting overall response rates of 55.6% and complete response rates of 44.4%. It works by activating the body's T-cells to target and kill cancerous B-cells, and has been conditionally approved for use in the USA for certain DLBCL patients. ^{1 2 3 4 5}

Is Epcoritamab safe for humans?

Epcoritamab has been tested in patients with certain types of lymphoma and has shown a manageable safety profile. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure), injection-site reactions, infections, and low white blood cell counts, but these were mostly mild and resolved without stopping treatment. ^{1 2 3 4 5}

How is the drug Epcoritamab unique for treating diffuse large B-cell lymphoma?

Epcoritamab is unique because it is a bispecific antibody that engages T-cells to target and kill cancerous B-cells, and it is administered subcutaneously (under the skin), which is different from many traditional intravenous treatments. This drug has shown effectiveness even in patients who have not responded to other CD20-targeted therapies. ^{1 2 3 4 5}

Research Team

Joseph M Tuscano

Principal Investigator

University of California, Davis

Eligibility Criteria

This trial is for patients with large B-cell lymphoma that has either returned after treatment (relapsed) or hasn't responded to previous treatments (refractory). Participants should have a type of lymphoma that can potentially respond to the drugs being tested. Specific eligibility criteria are not provided, but typically include factors like age, overall health, and the stage of cancer.

Inclusion Criteria

Measurable disease via diagnostic quality CT or PET/CT

ALT ≤ 3 x ULN

AST ≤ 3 x ULN

Exclusion Criteria

My cancer has spread to my brain or its coverings.

I have a confirmed autoimmune disease.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-AutoHCT Treatment

Participants receive epcoritamab subcutaneously and SOC platinum-based chemotherapy for up to 3 cycles

12 weeks

4 visits per cycle (in-person)

AutoHCT

Participants undergo autologous hematopoietic cell transplantation

1 week

1 visit (in-person)

Post-AutoHCT/Consolidation

Participants receive epcoritamab for up to 12 cycles post-transplant

48 weeks

4 visits per cycle initially, then reduced frequency

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 4 months

Treatment Details

Interventions

• Carboplatin
• Epcoritamab
• Oxaliplatin

Trial Overview The trial is testing epcoritamab combined with standard platinum-based chemotherapy (like RICE or Gem/Ox) and autologous hematopoietic cell transplant. Epcoritamab is designed to help the immune system target and kill lymphoma cells by binding to specific proteins on T cells and B cells.

Participant Groups

Group I: Treatment (epcoritamab, SOC chemotherapy, autoHCT) Experimental Treatment 11 Interventions

See Detailed Description

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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, 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, 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]

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, 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]

References

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

Epcoritamab: First Approval. [2023]

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. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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