Epcoritamab + Loncastuximab Tesirine for B-Cell Lymphoma

(EPCOR+LONCA Trial)

Overseen By Juan Alderuccio, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Miami

Must be taking: Anti-CD20, Anthracyclines

Must not be taking: CAR-T, AntiCD20XCD3

Disqualifiers: CNS lymphoma, Cardiac disease, 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: 1

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for individuals with B-cell lymphoma that has returned or resisted treatment. Researchers are investigating whether combining Epcoritamab (a type of immunotherapy) and Loncastuximab Tesirine (an antibody-drug conjugate) can effectively target and reduce cancer cells. The goal is to determine if this combination is safe and effective for patients. Individuals with difficult-to-treat B-cell lymphoma, especially those who have experienced recurrence after treatment, might be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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, if you are on glucocorticoid treatment, it must be reduced to a maximum of 25 mg daily in the last 14 days before starting the trial.

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

Studies have shown that both Epcoritamab and Loncastuximab Tesirine have been used separately to treat B-cell lymphoma with some success. Specifically, patients reported feeling better when Epcoritamab was used for relapsed large B-cell lymphoma, suggesting it might be well-tolerated. Loncastuximab Tesirine demonstrated a 48% response rate in patients with relapsed B-cell lymphoma, indicating it is effective and generally safe.

This trial tests the combination of these two drugs. As it is in a mid-stage phase, some evidence suggests it might be safe, but researchers are still gathering more data to confirm this. Participants may experience some side effects, but the goal is to determine if the combination works well without causing too many problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Epcoritamab and Loncastuximab Tesirine for B-Cell Lymphoma because these treatments introduce innovative approaches to fighting cancer cells. Unlike standard therapies like chemotherapy and monoclonal antibodies, Epcoritamab is a bispecific antibody that simultaneously targets CD3 on T-cells and CD20 on B-cells, effectively recruiting the body's own immune system to attack lymphoma cells. Loncastuximab Tesirine, on the other hand, is an antibody-drug conjugate that delivers a powerful chemotherapy agent directly to the cancer cells, minimizing damage to healthy cells. This dual-action approach not only offers a targeted attack on cancer cells but also aims to reduce the side effects commonly associated with traditional treatments.

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

In this trial, participants will receive a combination of Epcoritamab and Loncastuximab Tesirine to treat B-cell lymphoma. Research has shown that both Epcoritamab and Loncastuximab Tesirine are promising treatments. Epcoritamab has been effective for patients whose large B-cell lymphoma has returned or hasn't responded to other treatments, demonstrating a strong response rate. Loncastuximab Tesirine has also shown effectiveness, particularly for treating diffuse large B-cell lymphoma, a type of non-Hodgkin lymphoma, when it has relapsed or is resistant to treatment. The trial aims to determine if the combination therapy can offer even greater benefits than each treatment alone, potentially leading to better results in reducing or eliminating lymphoma cells. ^{1 2 3 6 7}

Who Is on the Research Team?

Juan Alderuccio, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

Adults with relapsed/refractory large B-cell lymphoma who've had at least one prior treatment including anti-CD20 antibody and anthracycline. They must have a life expectancy of 12 weeks, manageable health status (ECOG PS 0-2), and adequate organ function. HIV-positive patients can join under certain conditions. Exclusions include CNS lymphoma involvement, pregnancy, severe chronic diseases, recent major surgery complications, active hepatitis B or C infection, previous CAR-T therapy or stem cell transplant.

Inclusion Criteria

Patients with history of human immunodeficiency virus (HIV) are eligible under specific conditions

I can care for myself and am up and about more than 50% of my waking hours.

Ability to comply with the trial protocol

Exclusion Criteria

My lymphoma affects my brain or spinal cord.

Pregnant or breast feeding

I do not have severe lung disease or other serious conditions that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive up to 4 cycles of combination EPCOR and LONCA therapy, followed by an additional 8 cycles of EPCOR therapy

12 months

Cycles 1-3: 21 days each, Cycles 4-12: 28 days each

Follow-up

Participants are monitored for safety and effectiveness after treatment

14 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

36 months

What Are the Treatments Tested in This Trial?

Interventions

• Epcoritamab
• Loncastuximab Tesirine

Trial Overview The trial is testing the combination of two drugs: Epcoritamab and Loncastuximab Tesirine for treating large B-cell lymphoma that has returned after treatment or hasn't responded to it. The goal is to see if this drug duo can safely reduce or eliminate cancer cells in participants.

How Is the Trial Designed?

Group I: EPCOR in combination with LONCA Treatment Group Experimental Treatment 2 Interventions

Participants in the Epcoritamab (EPCOR) in combination with Loncastuximab (LONCA) treatment group will receive up to 4 cycles of combination EPCOR and LONCA therapy, and an additional 8 cycles of EPCOR therapy, for a total of twelve treatment cycles. Cycles 1 through 3 last 21 days each; cycles four through 12 last 28 days each. Protocol therapy will last approximately 12 months. Total participation duration is approximately 3 years.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

ADC Therapeutics S.A.

Industry Sponsor

Trials

32

Recruited

2,700+

Genmab

Industry 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

Published Research Related to This Trial

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]

Loncastuximab tesirine is an antibody-drug conjugate that targets B cell lymphomas, specifically approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of treatment.

The drug works by using an anti-CD19 antibody to deliver a DNA-alkylating agent directly to B cells, enhancing its efficacy in targeting cancer cells while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. Lee, A.[2021]

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 a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

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]

In a phase 2 trial involving 145 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), loncastuximab tesirine demonstrated a significant overall response rate of 48.3%, indicating its effectiveness as a treatment option for this challenging patient population.

The treatment was associated with an acceptable safety profile, with serious adverse events occurring in 39% of patients, but none were directly linked to loncastuximab tesirine, suggesting it may be a safe option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Caimi, PF., Ai, W., Alderuccio, JP., et al.[2021]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.3% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma during the phase II LOTIS-2 trial, indicating its efficacy as a treatment option.

The drug demonstrated a tolerable safety profile with common side effects including neutropenia and thrombocytopenia, and no new safety concerns were identified in the phase II trial, suggesting it is safe for further testing in various non-Hodgkin lymphoma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. Zurko, J., Hamadani, M.[2021]

Loncastuximab tesirine-lpyl, an anti-CD19 antibody-drug conjugate, has shown a 48.6% overall response rate in patients with relapsed, refractory diffuse large B-cell lymphoma, indicating its efficacy as a treatment option.

The drug has a tolerable safety profile, with common side effects including neutropenia and thrombocytopenia, leading to its recent FDA approval for treating this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma: a review of clinical data. Furqan, F., Hamadani, M.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07197307

Study Details | NCT07197307 | Combining Loncastuximab ... This is a phase II study designed to evaluate the toxicity and efficacy of the combination of loncastuximab tesirine and epcoritamab in ...

2. ashpublications.org ashpublications.org/blood/article/146/18/2177/546196/Real-world-outcomes-of-patients-with-aggressive-B

Real-world outcomes of patients with aggressive B-cell ... The overall response rate (ORR) for epcoritamab and glofitamab was 51% (23% complete response, [CR]) and 53% (30% CR), respectively. Median ...

3. nature.com nature.com/articles/s41408-024-01195-4

Outcomes with loncastuximab tesirine following CAR T-cell ... OS at 12 months was 95%. In this study, we found that lonca monotherapy was an effective treatment option in R/R DLBCL in 3 L and 4 L settings ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11588654/

Epcoritamab in relapsed/refractory large B-cell lymphoma We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall ...

5. withpower.com withpower.com/trial/phase-2-lymphoma-b-cell-5-2025-289eb

Epcoritamab + Loncastuximab Tesirine for B-Cell Lymphoma Loncastuximab Tesirine has demonstrated effectiveness in treating relapsed or refractory DLBCL, with a notable response rate in clinical trials.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11873705/

Loncastuximab in high-risk and heavily pretreated relapsed ... The LOTIS-2 study reported an overall response rate (ORR) of 48% and a complete response rate (CRR) of 25% with a median progression-free survival and median ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2152265023021833

Improvements in Patient-Reported Outcomes in Relapsed ... Patient-reported outcomes were evaluated in EPCORE NHL-1 in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab ...