Genmab Announces Epcoritamab Monotherapy and Epcoritamab-Based Combination Regimens Demonstrate High Response Rates in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)

Genmab A/S (Nasdaq: GMAB) today announced new data from two studies evaluating epcoritamab, a T-cell engaging antibody administered subcutaneously, in the first-line (1L) treatment of patients with diffuse large B-cell lymphoma (DLBCL) who may have limited treatment options due to advanced age or multiple health conditions. Results from the Phase 2 EPCORE^® DLBCL-3 study showed an overall response rate (ORR) of 67% and a complete response (CR) rate of 58% with epcoritamab monotherapy in elderly patients with newly diagnosed DLBCL. In the Phase 1b/2 EPCORE NHL-2 study, epcoritamab plus rituximab plus dose-attenuated cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) demonstrated an ORR of 93% and a CR rate of 86% in elderly patients with newly diagnosed DLBCL.

The results from both studies were presented in two poster presentations (abstracts PS2082 and PF1007) at the European Hematology Association (EHA) 2026 Congress held in Stockholm, Sweden, June 11-14. Additionally, the full EPCORE DLBCL-3 results have been simultaneously published in The Lancet Haematology.

EPCORE DLBCL-3 Results
The Phase 2 EPCORE DLBCL-3 study (abstract PS2082) evaluated the efficacy and safety of fixed-duration epcoritamab monotherapy in newly diagnosed CD20+ large B-cell lymphoma (LBCL) patients ineligible for anthracycline-based chemotherapy due to age (≥80 years) or comorbidities (≥75 years with comorbidities). Among 66 enrolled patients, the median age was 82.5 years, and all had comorbid conditions (94% with ≥3 comorbidities). With a median follow-up of 21.9 months, epcoritamab monotherapy demonstrated responses in this population with high unmet medical need.

An ORR of 67% and a CR rate of 58% were observed in evaluable patients (n=66). Median time to response was 1.5 months, and median time to CR was 2.2 months. Notably, 11 of 17 patients with a partial response or stable disease at first assessment subsequently achieved a CR.

"For newly diagnosed elderly patients with diffuse large B-cell lymphoma and comorbidities, who are often excluded from standard curative chemotherapy and ineligible for doxorubicin, finding more options is paramount," said Umberto Vitolo, M.D. Candiolo Cancer Institute, FPO-IRCCS, Candiolo (Turin), Italy. "The EPCORE DLBCL-3 study showed that epcoritamab monotherapy offers robust data. Importantly, its safety profile, including cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, was consistent with expected rates in this fragile population with a high unmet medical need for new therapeutic options."

Responses were durable, with median duration of response (DOR) and duration of complete response (DOCR) not reached. At 12 months, an estimated 67% of responses and 73% of CRs remained ongoing. Median progression-free survival (PFS) was 13.0 months, while median overall survival (OS) was not reached; an estimated 43% of patients remained progression-free and 62% were alive at 18 months. High rates of minimal residual disease (MRD) negativity were observed, with 92% of evaluable responders achieving MRD negativity, typically by Cycle 3 Day 1 and sustained through Cycle 12 Day 1 in most patients.

The safety profile was consistent with expected rates in this elderly population. Cytokine release syndrome (CRS) occurred in 71% of patients, most commonly during Cycle 1, and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 18%. Infections of any grade occurred in 68% of patients (26% Grade ≥3), and neutropenia was reported in 16%, with no febrile neutropenia or clinical tumor lysis syndrome observed. Eight Grade 5 TEAEs occurred.

EPCORE NHL-2, Arm 8 Results
Arm 8 of the Phase 1b/2 EPCORE NHL-2 study (abstract PF1007) evaluated epcoritamab plus R-mini-CHOP in 28 newly diagnosed CD20+ DLBCL patients ineligible for full-dose R-CHOP due to age (≥75 years) or comorbidities (≥65 years with comorbidities). With more than two years of follow-up, fixed-duration epcoritamab plus R-mini-CHOP demonstrated high response rates, sustained MRD negativity and durable remissions.

An ORR of 93% and a CR rate of 86% were observed. Median DOR, DOCR, PFS, and OS were not reached. At two years, estimated DOR and DOCR rates were 79%, while estimated PFS and OS rates were 76% and 82%, respectively.

“The EPCORE NHL-2 Arm 8 results are very encouraging, showing that combining epcoritamab with R-mini-CHOP led to high overall response rates and complete response rates, rapid and sustained minimal residual disease negativity, and durable remissions in this population,” said David Belada, M.D., Department of Internal Medicine—Haematology, Charles University, Hospital and Faculty of Medicine, Hradec Králové, Czech Republic. “These outcomes, alongside a consistent safety profile, potentially support the integration of epcoritamab with standard of care for these vulnerable patients, and highlight its broad utility in combinations across a range of disease settings and patient populations."

Rapid and sustained MRD negativity was observed, with 95% of evaluable patients achieving MRD negativity, including high rates in high-risk subgroups. Outcomes compared favorably with historical results for R-mini-CHOP alone.

The safety profile was consistent with prior reports and the known safety profiles of epcoritamab and R-mini-CHOP. The most common Grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia (54%), serious infections (33%) and anemia (14%). Most Grade ≥3 serious infections occurred during the first six cycles of treatment with R-mini-CHOP coadministration. TEAEs led to epcoritamab discontinuation in three patients (11%).

“Genmab is committed to evaluating epcoritamab as a potential treatment option in earlier lines of therapy for patients who traditionally struggle with aggressive treatment," said Dr. Judith Klimovsky, Executive Vice President and Chief Development Officer of Genmab. "The robust data observed in both the monotherapy and combination approaches reinforce our vision of making epcoritamab a foundational therapy across the spectrum of B-cell malignancies. These Phase 2 results support our ongoing commitment to addressing the significant unmet medical needs of elderly and comorbid patients, as we seek to identify effective, less intensive and tolerable options."

About Diffuse Large B-Cell Lymphoma
Diffuse large B-cell lymphoma (DLBCL) DLBCL is the most common type of non-Hodgkin lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases.^i,ii DLBCL can arise in lymph nodes as well as in organs outside of the lymphatic system, occurs more commonly in the elderly and is slightly more prevalent in men.^iii,iv DLBCL is a fast-growing type of NHL, a cancer that develops in the lymphatic system and affects B-cell lymphocytes, a type of white blood cell. For many people living with DLBCL, their cancer either relapses, which means it may return after treatment, or becomes refractory, meaning it does not respond to treatment. Although new therapies have become available, treatment management can remain a challenge.^iv,v

About the EPCORE^® DLBCL-3 Trial
EPCORE DLBCL-3 (NCT05660967) is an open-label, randomized, global, Phase 2 trial to evaluate the efficacy and safety of epcoritamab as monotherapy or in combination with lenalidomide as first-line therapy for anthracycline-ineligible subjects with diffuse large B-cell lymphoma (DLBCL). This is a 2-stage trial. In Stage 1, eligible patients were randomized to either epcoritamab monotherapy or epcoritamab plus lenalidomide. In Stage 2, additional patients were enrolled to the epcoritamab monotherapy arm. Each treatment cycle is 28 days. Patients will receive a maximum of 12 cycles (up to 1 year) of treatment. The primary objective is to evaluate the clinical efficacy of epcoritamab monotherapy or epcoritamab and lenalidomide. The primary endpoint is to achieve a complete response rate determined by Lugano criteria. Additional secondary endpoints include overall response rate, duration of response, duration of complete response, rate of minimal residual disease negativity, progression-free survival and overall survival.

More information on this trial can be found at www.clinicaltrials.gov/.

About the EPCORE^® NHL-2 Trial
EPCORE NHL-2 (NCT04663347) is a Phase 1b/2 open-label interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab as a monotherapy and in combination with other standard of care agents in patients with B-cell non-Hodgkin lymphoma (B-NHL). The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion). The primary objective of Part 1 is safety, and the primary goal of Part 2 is preliminary efficacy. The primary efficacy endpoint is overall response rate (ORR) based on best overall response per Lugano criteria. MRD negativity was assessed as a secondary endpoint.

More information on this trial can be found at www.clinicaltrials.gov.

About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology and administered subcutaneously. Genmab's DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to elicit an immune response toward target cell types. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T-cell-mediated killing of CD20+ cells.^vi

Epcoritamab (approved under the brand name EPKINLY^® in the U.S. and Japan, and TEPKINLY^® in the EU) has received regulatory approval in certain lymphoma indications in more than 65 territories. Where approved, epcoritamab is a readily accessible therapy. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies share commercial responsibilities in the U.S. and Japan, with AbbVie responsible for further global commercialization. Both companies will pursue additional international regulatory approvals for the investigational relapsed or refractory (R/R) follicular lymphoma (FL) indication and additional approvals for the R/R diffuse large B-cell lymphoma (DLBCL) indication.

Genmab and AbbVie continue to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes several Phase 3, open-label, randomized trials, including a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658), and a trial evaluating epcoritamab in combination with lenalidomide and rituximab (R²) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit www.clinicaltrials.gov for more information.

What is EPKINLY?
EPKINLY is a prescription medicine used to treat adults with:

• certain types of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma that has come back (relapsed) or that did not respond (refractory) after 2 or more treatments.
• follicular lymphoma (FL) that has come back or that did not respond to previous treatment, together with lenalidomide and rituximab
• follicular lymphoma (FL) that has come back or that did not respond after 2 or more treatments.

EPKINLY for the treatment of DLBCL 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 SAFETY INFORMATION
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 lead to death. 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 serious, and 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 may be hospitalized after receiving their first full dose of EPKINLY on Day 15 of Cycle 1 due to the risk of CRS and neurologic problems.

People with FL may be hospitalized after receiving their first full dose of EPKINLY on Day 22 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, feeling weak or generally unwell, or confusion.
• 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 and lymphopenia), 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.

The most common side effects of EPKINLY when used alone in DLBCL or high-grade B-cell lymphoma or FL include CRS, injection site reactions, tiredness, muscle and bone pain, fever, diarrhea, COVID-19, rash, and stomach-area (abdominal) pain. The most common severe abnormal laboratory test results with EPKINLY when used alone include decreased white blood cells, decreased red blood cells, and decreased platelets.

The most common side effects of EPKINLY when used together with lenalidomide and rituximab in FL include rash, upper respiratory tract infections, tiredness, injection site reactions, constipation, diarrhea, CRS, pneumonia, COVID-19, and fever. The most common severe abnormal laboratory test results with EPKINLY when used together with lenalidomide and rituximab include decreased white blood cells and decreased platelets.

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 Medication Guide, including Important Warnings.

About Genmab
Genmab is an international biotechnology company dedicated to improving the lives of people with cancer and other serious diseases through innovative antibody medicines. For over 25 years, its passionate, innovative and collaborative team has advanced a broad range of antibody-based therapeutic formats, including bispecific antibodies, antibody–drug conjugates (ADCs), immune-modulating antibodies and other next-generation modalities. Genmab’s science powers eight approved antibody medicines, and the company is advancing a strong late-stage clinical pipeline, including wholly owned programs, with the goal of delivering transformative medicines to patients.

Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit Genmab.com and follow us 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.

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