Epkinly (epcoritamab-bysp) / Genmab, AbbVie - LARVOL DELTA

Venetoclax and Obinutuzumab Followed by Epcoritamab for the Treatment of Untreated Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, LonGEVity Trial (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: City of Hope Medical Center | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2028 ➔ Jun 2029 | Trial primary completion date: Aug 2028 ➔ Jun 2029

Enrollment open • Trial completion date • Trial primary completion date • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

Phase ib study to assess the efficacy and safety of epcoritamab in relapsed or refractory post-transplant lymphoproliferative disorder (ASH 2025) - P1 | "In SOT recipients with PTLD who progress following risk-adapted rituximab and front-line chemoimmunotherapy, clinical outcomes are very poor. A maximum of 26 patients will be treated with subcutaneous epcoritamab utilizing a Fleming Two-Stage design with a one-sided error rate of 5% and 80% power to detect an objective response rate of 50% (null hypothesis 20% response rate). Exploratory objectives will evaluate the peripheral blood immunophenotype changes through the course of treatment with epcoritamab, describe the relationship of tumor microenvironment characteristics with clinical response to epcoritamab, characterize Epstein-barr virus (EBV) methylation alterations in EBV positive PTLDs treated with epcoritamab, and describe the relationship between metabolic tumor volume at time of epcoritamab initiation and disease response."

Clinical • P1 data • Post-transplantation • B Cell Lymphoma • Bone Marrow Transplantation • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Solid Organ Transplantation • Transplantation

Phase IB/II trial of epcoritamab plus ibrutinib in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (ASH 2025) - P1/2 | "Further, we will examine tumor samples obtained before starting treatment and at relapse/progression to explore aspects of the microenvironment that may contribute to treatment failure. Study status: The study is currently enrolling patients."

Clinical • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Leukemia • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • BCL2 • BCL6

Hematotoxicity and immune deficits with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma (ASH 2025) - "Among NHL cohorts, the BsAb distribution was: 7 glofitamab, 6 mosunetuzumab, 5 epcoritamab, and 4 odronextamab. Among MM cohorts, 6 received teclistamab, 3 talquetamab, 1 teclistamab and talquetamab, 2 elranatamab, 2 linvoseltamab and 1 etentamig (ABBV-383)... Cytopenias affect a substantial proportion of patients treated with BsAbs, particularly in MM and in NHL with combination regimes. These findings support the need for systematic hematologic monitoring, IG surveillance and tailored pre-emptive strategies to mitigate infection risk.This study represents the first and most comprehensive meta-analysis of hematotoxicity and immune deficits with BsAbs, establishing a benchmark across clinical settings."

Retrospective data • Review • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

Cardiovascular adverse events associated with bispecific antibodies in Relapsed/Refractory hematologic malignancies: A comprehensive systematic review and meta-analysis (ASH 2025) - "The study included seven bispecific antibodies (BsAbs) : blinatumomab , mosunetuzumab , elranatamab , epcoritamab , glofitamab , talquetamab , and teclistamab . While bispecific antibodies (BsAbs) show promising results in managing R/R hematologic malignancies, their use can lead to significant cardiac adverse effects, including tachycardia, arrhythmias, and hypotension. To mitigate these risks, a multidisciplinary approach—incorporating vigilant cardiac monitoring, preventive strategies, and prompt intervention—is essential for optimizing patient care and treatment success. Risk of Bias was relatively low."

Adverse events • Retrospective data • Review • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Hypertension • Hypotension • Lymphoma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Oncology

Effectiveness of epcoritamab in a heterogeneous population with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) including post-chimeric antigen receptor T-cell therapy (CAR T) patients: Insights from the real-world epcoritamab patient characteristics and outcomes research (Real-EPCOR) study (ASH 2025) - "Encouraging ORRs among those who received ≥2 cycles of epcor or had prior CAR T suggest that epcor monotherapy may provide clinical benefit even in difficult-to-treat pts in the real-world setting. Ongoing real-world survival analyses will inform the optimal use of epcor within the evolving treatment landscape of R/R DLBCL."

CAR T-Cell Therapy • Clinical • HEOR • Heterogeneity • Real-world • Real-world evidence • B Cell Lymphoma • Cardiovascular • Diabetes • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma

Incidence of second primary malignancies (SPMs) following bispecific antibody (BsAb) therapy for lymphoid malignancies: A descriptive analysis of clinical trials (ASH 2025) - "Included agents were blinatumomab (CD19×CD3), glofitamab, mosunetuzumab, epcoritamab, and odronextamab (all CD20×CD3), as well as elranatamab, teclistamab, and linvoseltamab (BCMA×CD3), and talquetamab (GPRC5DxCD3). Notably, some reported cases may represent disease progression rather than true SPMs. However, limited follow-up duration across trials warrants continued long-term surveillance, particularly as agents move to frontline settings where longer survival may reveal delayed malignancies."

Clinical • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lung Cancer • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Comparative analysis of fatal serious adverse events associated with FDA-approved bispecific antibodies in hematologic malignancies (ASH 2025) - " Using the FDA Adverse Events Reporting System (FAERS) public dashboard case-listing feature up to Q2 2025, individual reports listings with death as an outcome were extracted for all FDA-approved BsAbs/BiTEs: blinatumomab, glofitamab, epcoritamab, teclistamab, elranatamab, and talquetamab. The FAERS-based analysis aligns with literature on BsAb/BiTEs toxicities: CRS and infections are consistently reported fatal SAEs, with ICANS more notable in BCMA-targeting agents. Notably, our study also reveals underappreciated signals: cardiovascular fatal events, rare neurological syndromes beyond ICANS, and opportunistic infections—which are not prominently featured in the literature but appear in real-world fatal outcomes. These findings highlight both expected and emerging fatal toxicity patterns across FDA-approved BiTEs/BiAbs."

Adverse events • Serious adverse event • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • Septic Shock

Toxicity profile of epcoritamab and glofitamab in aggressive B-cell lymphoma: A real-world analysis of CRS and icans in a single-center cohort (ASH 2025) - "In this real-world cohort, rates of CRS were comparable, whereas ICANS incidence was slightly higher compared to pivotal trials, possibly due to broader patient eligibility, including older individuals and those with comorbidities or CNS involvement. Elevated baseline CRP predicted higher CRS severity, underscoring systemic inflammation as a driver of CRS. ICANS appeared slightly more common and were significantly associated with preexisting CNS involvement and baseline anemia, indicating vulnerability related to neurologic reserve or marrow function."

Clinical • IO biomarker • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Cardiovascular • Congestive Heart Failure • Coronary Artery Disease • Diabetes • Diabetic Nephropathy • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Metabolic Disorders • Neutropenia • Non-Hodgkin’s Lymphoma • Renal Disease • CD20 • CRP

Operational efficiencies and cost savings of using one bispecific antibody FDA-approved for both R/R 3L+ DLBCL and FL (ASH 2025) - "Utilizing a single bispecific antibody for the treatment of both 3L+ R/R DLBCL and FL can yield substantial operational and financial benefits in terms of staff time and direct financial cost savings for oncology practices. This approach reduces complexity across clinical, educational, administrative, and procurement workflows, supporting a more streamlined, resource-efficient care model. As the only bsAb currently approved by the FDA for both R/R 3L+ DLBCL and FL, epcoritamab can deliver value not only through improved clinical efficacy but also by enhancing operational efficiency."

HEOR • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Effectiveness and safety of bispecific antibodies in relapsed/refractory diffuse large B-cell lymphoma (DLBCL): A systematic review and meta-analysis (ASH 2025) - " Twelve eligible studies involving 744 patients were included, primarily evaluating glofitamab (6 studies), epcoritamab (2), mosunetuzumab (2), and odronextamab (2). Bispecific antibodies offer a promising therapeutic approach for relapsed/refractory DLBCL, particularly in heavily pretreated or CAR-T-ineligible patients. These findings support their expanding role in clinical practice and highlight the need for further real-world evidence. Multi-national randomized controlled trials with longer follow-up are needed to establish durability and optimize treatment sequencing."

Retrospective data • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Physicians perceptions of fixed-duration epcoritamab + lenalidomide and rituximab regimens in relapsed/refractory follicular lymphoma: Insights from the epcore NHL-2 trial (ASH 2025) - "Before reviewing trial data, despite 40% reporting BsAb use, only 29% reported they would select BsAbs (i.e., mosunetuzumab, epcoritamab) as their preferred 3L regimen for a hypothetical patient with R/R FL (65-year-old male, stage III, and an ECOG PS of 1 who received R-CHOP in 1L and bendamustine + rituximab in 2L), and most respondents preferred CAR T therapy (42%) for this patient. U.S. oncologists demonstrated increased interest in the fixed duration of ER2 following review of EPCORE NHL-2 data, with a notable shift in preference from CAR T to BsAbs in earlier lines of treatment for R/R FL. The regimen's defined treatment duration and potential for use in 2L settings were key drivers of interest. These findings suggest that ER2 may offer a clinically attractive alternative to existing therapies, particularly for patients' ineligible for CAR T or those seeking outpatient, time-limited options."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Optim.AI™ 2.0: Functional precision platform for identifying effective immunotherapy combinations in DLBCL (ASH 2025) - "PBMCs were added to tumor cells at a fixed effector-to-target ratio, and Optim.AI 2.0 combinatorial drug sensitivity testing plates were applied to the co-culture system, with up to 12 FDA-approved drugs, including monoclonal antibodies (rituximab, obinutuzumab), antibody-drug conjugates (polatuzumab), bispecific antibodies (epcoritamab, glofitamab), targeted small-molecule inhibitors (venetoclax, everolimus, zanubrutinib), and cytotoxic chemotherapies (gemcitabine, oxaliplatin, cyclophosphamide, doxorubicin). This study demonstrates the feasibility of Optim.AI™ 2.0, an enhanced co-culture-based platform which provides a physiologically relevant and scalable approach to functionally evaluate immunotherapy drug sets. With further validation, Optim.AI™ 2.0 holds strong potential to support clinical decision-making and expand the use of immunotherapies in DLBCL."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Sarcoma • Solid Tumor

Cardiovascular safety profile of CD20 × CD3 bispecific antibodies compared to immune-checkpoint inhibitors: A faers analysis, 2014–2025 (ASH 2025) - "Background: Bispecific T-cell engagers (BTEs) have evolved from CD19 × CD3 constructs such as blinatumomab to newer CD20 × CD3 agents, including mosunetuzumab, glofitamab, and epcoritamab. CD20 × CD3 bispecifics are associated with a distinct arrythmia signal, more frequent and earlier than that observed with ICIs. However, overall arrhythmia reporting has declined over time, likely reflecting improved mitigation strategies such as step-up dosing and early monitoring. Nonetheless, the absolute incidence (2.8%) exceeds that seen with ICIs, supporting baseline ECG and rhythm surveillance during CD20 BTE initiation."

Checkpoint inhibition • Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders • Inflammation • Oncology • Venous Thromboembolism • CD20 • ROR1

Real-world descriptive analysis of the use of bispecific t cell engagers (BiTEs) in the treatment of hematological malignancies in Qatar: A state-wide retrospective cohort study (ASH 2025) - "Nevertheless, in r/r multiple myeloma (MM) elranatamab and teclistamab have been used to target BCMA. Another BiTE targeting CD20 used in r/r follicular lymphoma (FL) such as mosunetuzumab, and glofitamab in r/r diffuse large B cell lymphoma (DLBCL), while epcoritamab has been approved in both indications (Shouse G., 2025)...Method This is a descriptive retrospective cohort study, including all adult hematological patients who were treated with BiTEs: epcoritamab, glofitamab, blinatumomab, and teclistamab...Despite the small sample size and the study design, our findings nearly comply with primary literature that BiTEs serve as a promising therapeutic alternative for patients with relapsed or refractory disease, particularly those who have exhausted other modalities. However, the high incidence of reported adverse drug reactions (ADRs), including severe toxicities such as CRS and ICANS, highlights the need for robust and careful strategies for safety and tolerability..."

Real-world • Real-world evidence • Retrospective data • Acute Lymphocytic Leukemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma

Epcoritamab monotherapy provides superior efficacy vs non–anthracycline-containing regimens in newly diagnosed elderly DLBCL patients deemed unsuitable for anthracycline-containing regimens: A match-adjusted comparative efficacy analysis (ASH 2025) - P2 | "Non-AC CITs included rituximab (R)-cyclophosphamide, doxorubicin, vincristine, prednisone [R-CEOP]/R-cyclophosphamide, vincristine, prednisone [R-CVP]/R-cyclophosphamide, etoposide, prednisone, procarbazine [R-CEPP]), bendamustine and rituximab (BR), and other combination regimens. Fixed-duration epcor mono demonstrated significantly superior OS vs non-AC regimens in newly diagnosed elderly and/or frail DLBCL pts deemed unsuitable for anthracyclines. These findings support epcor mono as a potential 1L chemo-free treatment option for newly diagnosed DLBCL pts unsuitable for AC regimens."

Clinical • Monotherapy • Diffuse Large B Cell Lymphoma • Large B Cell Lymphoma • Palliative care

Bridging the CART gap: Epcoritamab as a feasible option for relapsed/refractory DLBCL in CART-inaccessible regions - "the argentine experience" (ASH 2025) - "The use of BsAbs as a bridge to consolidation (mean 4 cycles) is a viable non-standard option for countries where their high costs make them unaffordable. Proper management of adverse events such as infections and hypogammaglobulinemia is crucial for improving safety and survival outcomes in these high-risk patients."

Diffuse Large B Cell Lymphoma • Hematological Disorders • Infectious Disease • Inflammation

Real-world outcomes of epcoritamab in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) following CAR T-cell therapy: A multicenter retrospective study from the trinetx global network (ASH 2025) - "The analysis included data from 172 million patients across 151 healthcare organizations worldwide, predominantly academic centers in the U.S. Eligible patients had a confirmed diagnosis of R/R DLBCL, received ≥2 prior lines of systemic therapy including CAR T-cell therapy (axicabtagene ciloleucel or lisocabtagene maraleucel), were treated with epcoritamab, had an ECOG performance status of 0–2, and had ≥30 days of follow-up...Grade 3–4 CRS and ICANS occurred in ~4.1% of patients, and 25% received tocilizumab... In this real-world cohort, epcoritamab demonstrated favorable short-term survival in patients with R/R DLBCL following CAR T-cell therapy, mirroring results from the EPCORE NHL-1 trial. By limiting the cohort to patients with ECOG 0–2 and excluding prior transplant recipients, the study population closely resembled clinical trial eligibility. These findings support the broader applicability of epcoritamab in routine practice and highlight the importance of early..."

CAR T-Cell Therapy • Real-world • Real-world evidence • Retrospective data • Atrial Fibrillation • B Cell Lymphoma • Cardiovascular • Congestive Heart Failure • Diffuse Large B Cell Lymphoma • Heart Failure • Infectious Disease • Influenza • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Pneumonia • Respiratory Diseases • Thrombocytopenia

Phase II investigator-initiated trial of epcoritamab-lenalidomide in treatment naïve follicular lymphoma (ASH 2025) - No abstract available

P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma

EPCORE FL-2 Phase 3 trial of epcoritamab with rituximab and lenalidomide (R2) vs chemoimmunotherapy (CIT) in previously untreated follicular lymphoma (FL): Trial in progress (ASH 2025) - P1/2, P3 | "The current standard of care (SOC) for patients with previously untreated advanced FL with hightumor burden includes CIT, combining anti-CD20 monoclonal antibody (rituximab [R] or obinutuzumab[G]) with chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] orbendamustine [benda]). Arm A2 will address the contribution ofmaintenance therapy to outcomes of epcoritamab plus R2 treatment. This study is currently enrollingpatients globally in 32 countries."

P3 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma

Pooled analysis of early-Phase trials highlights robust activity of CD3-CD20 T-cell engagers in follicular lymphoma (ASH 2025) - "It was not feasible to compare monotherapy withcombination therapy trials due to limitations in the reported risk categories of patients enrolled.R/R FL: In the relapsed setting, Epcoritamab was included in 3 trials (one of which was incombination with lenalidomide and rituximab (R2)), Mosunetuzumab in 2, Glofitamab in 1, andOdronextamab in 1. This pooled analysis confirms that CD3-CD20 TCE therapies achieve high overall andcomplete response rates in FL. This is particularly seen in the frontline setting. Responses in R/R werealso clinically meaningful and durable, especially given that most trials enrolled patients with at least 2 ormore previous lines of therapy."

Retrospective data • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CD20

Epkinly: Regulatory submission for 1L DLBCL (based on EPCORE DLBCL-2 trial) in 2026 (Genmab A/S) - 2025 R&D Update and ASH Data Review: Regulatory submission for 2L+ DLBCL (based on EPCORE DLBCL-1 trial) in 2026; Regulatory approval for 2L + follicular lymphoma (based on EPCORE-FL-1 trial) in 2026

Approval • Filing • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Oncology

Epkinly: “Superior PFS with 79% risk reduction”; Follicular lymphoma (Genmab A/S) - 2025 R&D Update and ASH Data Review: “Higher response rates”

P3 data • Follicular Lymphoma • Hematological Malignancies • Oncology

Phase II investigator-initiated trial of epcoritamab-lenalidomide in treatment naïve follicular lymphoma (ASH 2025) - P1/2, P2 | "In the phase 1/2 trial (NCT04663347), epcoritamab pluslenalidomide and rituximab demonstrated high complete response (CR) rates in the 1L and R/R settings.Yet rituximab is associated with increased risk of infections, infusion related reactions, and costs. Analysis of additional samples will be presentedat the meeting.Summary/ConclusionOur results indicate that E-len is a safe and effective frontline chemotherapy-free regimen for treatmentnaïve FL pts, resulting in early and high CR rates. Longer follow-up will be needed to evaluate thedurability of these responses."

P2 data • Cardiovascular • Constipation • Febrile Neutropenia • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Nephrology • Neutropenia • Renal Disease • Respiratory Diseases • Venous Thromboembolism • CD20 • CD4 • CD8 • MYC

Health-related quality of life (HRQoL) in patients with relapsed/refractory follicular lymphoma treated with epcoritamab in combination with rituximab plus lenalidomide (E+R2): Primary results of the EPCORE FL-1 trial (ASH 2025) - P3 | "In the EPCORE FL-1 study, patients with R/R FL had relatively low symptom burden and highQoL at baseline. Despite the higher Grade 3/4 adverse events, patients treated with E+R2 maintainedtheir high QoL compared with those treated with R2 alone, complementing the improved efficacybenefits observed in the trial. These data show that the E+R2 regimen has the potential to be a best-in-class, novel chemotherapy-free standard of care in R/R FL and is associated with a manageable safetyprofile and maintains QoL."

Clinical • Combination therapy • HEOR • Follicular Lymphoma • Hematological Malignancies • Lymphoma