Epcoritamab Clinical Trials

What Is Epcoritamab?

Epcoritamab is an investigational drug currently being studied in clinical trials for various types of B-cell lymphomas and leukemias. It is a bispecific antibody, which is a synthetic protein designed to activate the body's immune system. Epcoritamab works by bringing T cells (a type of immune cell) close to cancer cells, thereby activating the T cells to target and kill the lymphoma or leukemia cells.

Clinical trials are evaluating epcoritamab as a potential treatment for conditions such as follicular lymphoma, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. The drug is being investigated both as a standalone therapy and in combination with other treatments. A total of 52 clinical trials have been initiated for epcoritamab, with the first trial starting in 2018 and the latest projected to conclude in 2026. These trials have enrolled a total of 7,477 participants.

Uses and Conditions Under Study

Epcoritamab is primarily under investigation for the treatment of various B-cell lymphomas and leukemias. These cancers originate from B lymphocytes, a type of white blood cell. As a bispecific antibody, epcoritamab is designed to help the immune system recognize and destroy these cancerous B cells.

Several types of lymphoma are being studied. Follicular Lymphoma, a slow-growing type, is being investigated in 7 trials. Diffuse Large B-Cell Lymphoma, a more aggressive form, is the focus of 6 trials, including a phase 2 study for patients who have relapsed or are refractory to prior therapy. Other lymphomas under study include Small Lymphocytic Lymphoma (5 trials), High-grade B-cell Lymphoma (4 trials), and general Lymphoma (4 trials). Additionally, Marginal Zone Lymphoma (4 trials), Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified (3 trials), Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified (3 trials), and Large B-cell Lymphoma (3 trials) are also being explored.

Beyond lymphomas, epcoritamab is also being evaluated for leukemias and other B-cell cancers. Chronic Lymphocytic Leukemia (CLL), a type of cancer affecting blood and bone marrow, is being studied in 3 trials. Furthermore, epcoritamab is being investigated in a phase 2 trial for participants with previously treated Waldenstrom Macroglobulinemia, a rare type of non-Hodgkin lymphoma that produces abnormal proteins.

Dosing

Epcoritamab is administered via subcutaneous injection. The dosing schedule often involves an initial "step-up" approach, where lower doses are given first, followed by full therapeutic doses. This method is used to manage potential side effects as the body adjusts to the medication.

One studied regimen involves initial step-up doses of 0.16 mg and 0.8 mg, followed by 12 mg administered weekly for three 21-day cycles. Another detailed schedule includes a step-up dose of 0.16 mg on Cycle 1 Day 1, followed by 0.80 mg on Cycle 1 Day 8. The first full dose of 48 mg is then given on Cycle 1 Day 15. For Cycles 2 through 4, 48 mg is administered on Days 1, 8, and 15. In Cycles 5 through 12, the 48 mg dose is given on Days 1 and 15. These specific dosing schedules are part of ongoing clinical investigations to determine the optimal and safest way to administer epcoritamab for various conditions.

Side Effects

Side effect data for Epcoritamab (GEN3009) comes from an open-label, first-in-human study (NCT04358458) in patients with relapsed or refractory B-cell non-Hodgkin lymphomas. This means there was no placebo group for comparison. The data describes categories of adverse events across various dose levels (A through G) in Part 1 of the study.

• The number of participants who experienced any treatment-emergent adverse events (TEAEs) ranged from 3 to 10 participants across the different dose levels.
• The number of participants who experienced serious TEAEs ranged from 0 to 10 participants across the different dose levels.
• Adverse events of special interest (AESI) were reported in 1 to 10 participants across the dose levels.
• Dose-limiting toxicities (DLTs) were observed in up to 3 participants in one dose level (Dose Level G), with no DLTs reported in other dose levels.
• Clinically significant laboratory abnormalities reported as TEAEs were seen in up to 2 participants in some dose levels.
• Dose delays and dose interruptions occurred in up to 10 participants in certain dose levels.
• Positive anti-drug antibodies (ADAs) were detected in up to 2 participants in some dose levels.

Specific individual side effects (e.g., fever, fatigue) are not detailed in the provided data; only categories of events are reported.

Clinical Trial Results

Clinical efficacy results for Epcoritamab (GEN3009) were evaluated in an open-label, first-in-human study (NCT04358458) involving patients with relapsed or refractory B-cell non-Hodgkin lymphomas. This trial included several dose levels (A through G) in Part 1, and no placebo group was used for comparison.

Response Rates

• The Objective Response Rate (ORR), which measures the percentage of patients whose cancer shrinks or disappears, varied across dose levels. The highest ORR was 66.7% in patients receiving Dose Level F. Other dose levels showed ORRs of 42.9% (Dose Level C), 37.5% (Dose Level E), and 33.3% (Dose Level D in S2).
• The Complete Response (CR) Rate, indicating that all signs of cancer disappeared, also varied. The highest CR rates were 33.3% in patients at Dose Level D (S2) and Dose Level F. Patients in Dose Level C achieved a CR rate of 28.6%.

Duration of Response and Survival

• The median Duration of Response (DoR), which is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading, was 15.9 months for patients in Dose Level C. Other reported median DoRs included 4.1 months (Dose Level G) and 1.4 months (Dose Level E).
• Median Progression-Free Survival (PFS), the time patients lived without their disease getting worse, ranged from 0.8 months to 4.3 months across the different dose levels. The longest median PFS was 4.3 months in patients receiving Dose Level C.
• Median Overall Survival (OS), the total time patients lived from the start of treatment, ranged from 6.6 months to 13.7 months across the dose levels where data was available. The longest median OS was 13.7 months in patients at Dose Level E, followed by 13.1 months in Dose Level F, and 10.9 months in Dose Level D (S1).

Currently Recruiting Trials

Epcoritamab is being investigated in numerous clinical trials to explore its potential in treating various types of B-cell lymphomas. These studies aim to understand how Epcoritamab works alone or in combination with other therapies to improve outcomes for patients.

One notable study, NCT07451652, is a Phase 2 trial enrolling 10 participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Researchers are evaluating whether a lower dose of Epcoritamab (12 mg) combined with Gemcitabine/Oxaliplatin (GemOx) can be effective for those who are candidates for autologous stem cell transplantation.

Another Phase 2 study, NCT06919939, sponsored by the University of Miami, is recruiting 26 participants with relapsed or refractory large B-cell lymphoma. This trial investigates the tolerability and effectiveness of combining Epcoritamab with Loncastuximab Tesirine to reduce or eliminate lymphoma cells.

For patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the LonGEVity trial (NCT07218510) is a Phase 2 study enrolling 33 participants. It tests the effect of venetoclax and obinutuzumab followed by Epcoritamab as an initial treatment.

The University of Washington is sponsoring a Phase 2 trial (NCT07097363) for 18 participants with aggressive B-cell non-Hodgkin lymphoma. This study assesses the safety and effectiveness of Epcoritamab when given with the EPOCH-R chemotherapy regimen.

A Phase 2 study (NCT06796998) is exploring Epcoritamab for patients with newly diagnosed marginal zone lymphoma (MZL), including extranodal, splenic, and nodal types. This trial aims to determine if Epcoritamab is beneficial for 25 participants in this setting.

For patients with relapsed or refractory primary diffuse large B-cell lymphoma of the Central Nervous System (CNS), a Phase 2 study (NCT06931652) is evaluating the efficacy and safety of Epcoritamab after treatment with rituximab and lenalidomide, with an enrollment target of 60 participants.

A large Phase 3 study (NCT06191744) sponsored by Genmab is enrolling 1095 participants with previously untreated follicular lymphoma. This trial compares subcutaneous Epcoritamab in combination with lenalidomide and rituximab (R2) against standard chemoimmunotherapy or R2 alone, assessing its safety and effectiveness.

Finally, a Phase 2 trial (NCT06238648) is comparing Epcoritamab to observation for 120 patients with B-cell lymphomas who are not in complete remission after CD19-directed CAR-T cell therapy, exploring its role as a consolidation treatment.

Where to Participate

Clinical trials for Epcoritamab are currently recruiting across a broad geographic area, offering opportunities for participation in many regions. These studies are active at 120 sites located in 84 cities across 34 states.

The cities with the highest number of recruiting sites include:

• New York, New York (8 sites)
• Boston, Massachusetts (7 sites)
• Seattle, Washington (4 sites)
• Columbus, Ohio (4 sites)
• Miami, Florida (3 sites)
• Salt Lake City, Utah (3 sites)
• Houston, Texas (3 sites)
• Philadelphia, Pennsylvania (3 sites)
• Louisville, Kentucky (2 sites)
• Newark, Delaware (2 sites)

Eligibility criteria for these trials generally specify an age range of 16-65 years, and participants of all genders are welcome. Healthy volunteers are not eligible to participate, but some studies do include children.

Development Timeline

The journey of Epcoritamab in clinical development began with its first trial initiated on August 10, 2018. Since then, the investigational drug has seen significant expansion in its research, with the latest trial projected to conclude in April 2026. This extensive research program has involved a total of 52 clinical trials, aiming to enroll approximately 7,477 participants.

Early development primarily focused on various B-cell lymphomas, including Small Lymphocytic Lymphoma, High-grade B-cell Lymphoma, Marginal Zone Lymphoma, Large B-cell Lymphoma, Chronic Lymphocytic Leukemia, and Diffuse Large B-Cell Lymphoma. The pipeline has steadily expanded to cover a wide spectrum of these conditions, including relapsed/refractory settings, newly diagnosed cases, and even as a consolidation therapy after other treatments like CAR-T cell therapy.

The development has progressed through various phases, with the majority of studies, 30, being Phase 2 trials. There are also 8 Phase 1/Phase 2 studies, 6 dedicated Phase 1 trials, and 6 large-scale Phase 3 trials underway, indicating a robust and advancing research program. Genmab has been a primary driver of this development, sponsoring 17 of the trials, alongside contributions from numerous academic institutions and other organizations.