Genmab Reports Encouraging Data for Epcoritamab Combination Therapy in R/R DLBCL Patients Suitable for ASCT

• New trial data indicates that the investigational treatment combining epcoritamab with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) achieved an 87% overall response rate (ORR) and a 65% complete response (CR) rate in patients battling relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
• The data further highlights epcoritamab’s potential to enhance the proportion of patients eligible for Autologous Stem Cell Transplantation (ASCT) when used in conjunction with salvage chemoimmunotherapy.
• These findings were presented during an oral session at the 30th European Hematology Association (EHA) Congress.

Copenhagen, Denmark – Shares of Genmab A/S (GMAB) are attracting attention today following the release of encouraging new data from the Phase 1b/2 EPCORE^® NHL-2 trial. Arm 10 (NCT04663347) is evaluating epcoritamab, a subcutaneously administered T-cell engaging bispecific antibody, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in adults with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are eligible for autologous stem cell transplantation (ASCT). The study revealed an impressive overall response rate (ORR) of 87%, with a complete response (CR) rate of 65% and a partial response (PR) of 23%. Moreover, the majority of patients (65%) proceeded to ASCT. After six months, an estimated 81% of responses were still ongoing, with 74% of patients remaining progression-free, and 100% of patients alive. These results, which were shared during an oral presentation at the 30th European Hematology Association (EHA) 2025 Congress, are generating buzz within the medical community.

The combination therapy’s safety profile appears manageable, with mainly low-grade cytokine release syndrome (CRS) and no treatment-emergent adverse events (TEAEs) leading to discontinuation. The most common TEAEs observed were neutropenia (74%), anemia (68%), and thrombocytopenia (68%). CRS occurred in 52% of patients, all of which were low grade (1/2) and resolved. One patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS; grade 1), which also resolved. Notably, no clinical tumor lysis syndrome was observed. Infections were reported in 18 patients (58%), with five (16%) classified as serious. Importantly, there were no Grade 5 TEAEs.

“These results are particularly encouraging because many of the patients in this study had high-risk disease, having progressed rapidly after initial treatment,” stated Dr. Raul Cordoba, MD, PhD, Head of the Lymphoma Unit at the Fundacion Jimenez Diaz University Hospital in Madrid, Spain. He added that, “This combination therapy of epcoritamab plus rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) offers a potential new treatment option for patients with relapsed/refractory diffuse large B-cell lymphoma, providing high response rates and a bridge to potentially curative autologous stem cell transplantation.”

Further analysis of the study data revealed compelling responses across different patient subgroups. Among patients who progressed within 12 months of first-line treatment (n=20), epcoritamab combined with R-ICE showed an 85% ORR and a 55% CR. For patients who progressed after 12 months from first-line therapy, the ORR was 91% and the CR was 82%. Additionally, patients with one prior line of therapy experienced an 88% ORR and a 68% CR, while those with more than one prior line of therapy achieved an 83% ORR and a 50% CR.

“The results from this trial highlight the potential of this investigational epcoritamab containing regimen, especially in patients who progress quickly after initial treatment, and reinforce our joint efforts with AbbVie to develop epcoritamab as a core therapy for B-cell lymphomas, especially as we develop epcoritamab in earlier lines of therapy and a broader patient population,” said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. She emphasized that Genmab’s “comprehensive EPCORE clinical trial program is dedicated to advancing epcoritamab as both monotherapy and in combination to address the significant unmet need in relapsed/refractory diffuse large B-cell lymphoma and other hematologic malignancies.”

It’s important to note that the use of epcoritamab + R-ICE in patients with R/R DLBCL eligible for ASCT is currently not approved. The safety and efficacy of epcoritamab as a combination therapy for DLBCL have not yet been established.

Diffuse Large B-Cell Lymphoma: A Deep Dive

DLBCL stands as the most prevalent type of non-Hodgkin’s lymphoma (NHL) worldwide, accounting for roughly 25-30% of all NHL cases. In the United States, approximately 25,000 new DLBCL diagnoses are made each year. While DLBCL can originate in lymph nodes, it can also affect organs outside the lymphatic system. The disease is more common in the elderly and slightly more prevalent in men. As a rapidly progressing form of NHL, DLBCL develops within the lymphatic system, impacting B-cell lymphocytes, a type of white blood cell. Despite the availability of new therapies, treatment management can still be challenging, particularly in cases of relapse or when the cancer becomes refractory, meaning it doesn’t respond to treatment.

EPCORE^® NHL-2 Trial: The Inside Story

The EPCORE NHL-2 trial is a Phase 1b/2 open-label interventional study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab, both as a single therapy and in combination with standard-of-care agents in patients with B-cell non-Hodgkin’s lymphoma (B-NHL). The trial is divided into two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). While the primary objective of Part 1 centers on safety, the key objective of Part 2 is to assess preliminary efficacy. The primary endpoint for this study was overall response rate (ORR), measured according to the best overall response based on Lugano criteria. MRD negativity was evaluated as a secondary endpoint.

Arm 10 of the EPCORE NHL-2 study enrolled 31 patients with R/R DLBCL who met the criteria for R-ICE and ASCT and had undergone at least one prior line of treatment. At the time of the data cutoff (December 18, 2024), the median follow-up was 11 months (ranging from 6 to 15 months). Among the 31 patients treated with epcoritamab 48 mg + R-ICE, 61% presented Ann Arbor stage III/IV disease, 42% had bulky disease measuring ≥7 cm, 81% had received one prior line of therapy (ranging from 1 to 3), and 65% had progressed within 12 months of their first-line treatment. For more information on this trial, visit www.clinicaltrials.gov (NCT: 04663347).

Understanding Epcoritamab

Epcoritamab is a groundbreaking IgG1-bispecific antibody created utilizing Genmab’s proprietary DuoBody^® technology, designed for subcutaneous administration. Genmab’s DuoBody-CD3 technology specifically targets cytotoxic T cells, triggering an immune response directed towards target cell types. Epcoritamab is engineered to simultaneously bind to CD3 on T cells and CD20 on B cells, effectively inducing T-cell-mediated killing of CD20+ cells.

Epcoritamab (marketed under the brand name EPKINLY^® in the U.S. and Japan, and TEPKINLY^® in the EU) has received regulatory approval for specific lymphoma indications in several regions. Where approved, epcoritamab offers a readily accessible therapy, eliminating the need for tumor burden reduction (“debulking”). This drug is being co-developed by Genmab and AbbVie as part of their oncology collaboration. These companies will share commercial responsibilities in the U.S. and Japan, with AbbVie assuming responsibility for worldwide commercialization. Moreover, both companies are actively pursuing additional international regulatory approvals for the investigational R/R FL indication and further approvals for the R/R DLBCL indication.

Genmab and AbbVie are continuing to evaluate the use of epcoritamab, both as a monotherapy and in combination with other treatments, across various lines of therapy for a range of hematologic malignancies. This includes five ongoing Phase 3, open-label, randomized trials. These trials include an evaluation of epcoritamab as a monotherapy for R/R DLBCL compared to investigator’s choice chemotherapy (NCT04628494), an investigation of epcoritamab in combination with R-CHOP for adult patients with newly diagnosed DLBCL (NCT05578976), an evaluation of epcoritamab combined with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), a comparison of epcoritamab in combination with rituximab and lenalidomide (R2) versus chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial assessing epcoritamab combined with R2 compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab have not been established for these investigational uses. Further details can be found at www.clinicaltrials.gov.

EPKINLY^® (epcoritamab-bysp) U.S. INDICATIONS & IMPORTANT SAFETY INFORMATION

What is EPKINLY?

EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.

Important Warnings—EPKINLY can cause serious side effects, including:

• Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
• Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.

People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.

Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.

EPKINLY can cause other serious side effects, including:

• Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
• Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.

Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.

In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.

These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).

Please see Full Prescribing Information and Medication Guide, including Important Warnings.

Globally, prescribing information varies; refer to the individual country product label for complete information.

About Genmab

Genmab, an international biotechnology firm, is driven by its core mission: to improve the lives of patients by developing novel and differentiated antibody therapeutics. For the past 25 years, its innovative and collaborative team has pioneered next-generation antibody technology platforms, leveraging translational, quantitative, and data sciences. This has resulted in a proprietary pipeline featuring bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators, and effector function-enhanced antibodies. By 2030, Genmab envisions transforming the lives of individuals battling cancer and other severe diseases with its groundbreaking antibody medicines.

Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with a global presence spanning North America, Europe, and Asia Pacific. Further information can be found at Genmab.com, and you can follow the company on LinkedIn and X.

This Media Release contains forward looking statements. The words “believe,” “expect,” “anticipate,” “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with preclinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products or technologies obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com and the risk factors included in Genmab’s most recent Annual Report on Form 20-F and other filings with the U.S. Securities and Exchange Commission (SEC), which are available at www.sec.gov. Genmab does not undertake any obligation to update or revise forward looking statements in this Media Release nor to confirm such statements to reflect subsequent events or circumstances after the date made or in relation to actual results, unless required by law.

Genmab A/S and/or its subsidiaries own the following trademarks: Genmab^®; the Y-shaped Genmab logo^®; Genmab in combination with the Y-shaped Genmab logo^®; HuMax^®; DuoBody^®; HexaBody^®; DuoHexaBody^®, HexElect^® and KYSO™. EPCORE^®, EPKINLY^®, TEPKINLY^® and their designs are trademarks of AbbVie Biotechnology Ltd.

ⁱ Engelberts PJ, et al. DuoBody-CD3xCD20 Induces Potent T-Cell-Mediated Killing of Malignant B Cells in Preclinical Models and Provides Opportunities for Subcutaneous Dosing. EBioMedicine. 2020;52:102625. doi: 10.1016/j.ebiom.2019.102625.