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

26 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination Epcoritamab and Loncastuximab Tesirine for B-Cell Lymphoma?

Epcoritamab has shown strong anti-tumor activity in B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL), by engaging T-cells to attack cancer cells. Loncastuximab Tesirine has demonstrated effectiveness in treating relapsed or refractory DLBCL, with a notable response rate in clinical trials. Both drugs have been individually effective in similar conditions, suggesting potential when combined. ^{1 2 3 4 5}

Is the combination of Epcoritamab and Loncastuximab Tesirine safe for humans?

Loncastuximab Tesirine has been shown to have an acceptable safety profile in clinical trials for B-cell non-Hodgkin lymphoma, with common side effects including low blood cell counts, fatigue, nausea, and liver enzyme changes. Epcoritamab has also demonstrated safety in early trials for B-cell lymphoma, but specific safety data for the combination of these two drugs is not available. ^{1 2 4 6 7}

What makes the drug combination of Epcoritamab and Loncastuximab Tesirine unique for treating B-cell lymphoma?

This drug combination is unique because Epcoritamab is a bispecific antibody that engages T-cells to target and kill cancerous B-cells, while Loncastuximab Tesirine is an antibody-drug conjugate that delivers a toxic payload directly to B-cells. Together, they offer a novel approach by combining two different mechanisms to attack B-cell lymphoma. ^{1 2 3 4 8}

What is the purpose of this trial?

The purpose of this study is to determine whether combining Loncastuximab Tesirine with Epcoritamab is tolerable and effective for reducing and/or eliminating lymphoma cells in the body.

Research Team

Juan Alderuccio, MD

Principal Investigator

University of Miami

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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-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]

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]

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]

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]

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]

References

1. 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]

2. England 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. [2021]

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

Epcoritamab: First Approval. [2023]

4. Spain pubmed.ncbi.nlm.nih.gov

Loncastuximab tesirine for diffuse large B-cell lymphoma. [2021]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. [2022]

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

Loncastuximab Tesirine: First Approval. [2021]