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

Therapy Sequencing in Relapsed/Refractory MCL (ICML 2025) - P1, P1/2, P2, P3 | "Although a direct comparison between them has only been performed for ibrutinib and temsirolimus [23], covalent BTK inhibitor (cBTKi) single agent therapy has been consolidated as the standard of care after first-line CIT. Moreover, to address cBTKi failure, two anti-CD19 CAR-T cell therapy products, brexucabtagene autoleucel [20, 21] and lisocabtagene maraleucel [22], and the first noncovalent BTKi, pirtobrutinib [19], have recently been approved...Liso-cel only FDA approved; CIT, chemoimmunotherapy options include BR, R-BAC, R-CHOP, R-DHAP or R-DHAOx, R-GEMOx, paliative options (avoid bendamustine pre-CART apheresis); pirtobrutinib, available after cBTKi failure in second-line (EMA) but third-line (FDA); RM, rituximab maintenance...Orelabrutinib [18] is licensed only in China...Of note, both acalabrutinib and zanubrutinib induce lower rates of atrial fibrillation, hypertension, and bleeding compared to ibrutinib in randomized studies..."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • PLCG2 • TP53

Advances in the Management of Relapsed/Refractory CLL and Richter Transformation (ICML 2025) - P=N/A, P2, P3 | "BRUIN CLL-321 is a phase 3, registrational study that evaluated pirtobrutinib compared to the investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) [23]...Nemtabrutinib is now being evaluated in the registrational, phase 3 BELLWAVE-010 trial (NCT05947851) for patients with R/R CLL, comparing nemtabrutinib plus venetoclax to venetoclax plus rituximab...An ongoing, open-label, first-in-human phase 1/2 study is evaluating the BTK degrader BGB-16673 as monotherapy in patients with R/R CLL [27, 28]...NX-2127 is an investigational, first-in-class BTK degrader currently being evaluated in a phase 1 trial for patients with relapsed or refractory B-cell malignancies, CLL [29, 30]...NX-5948 is another investigational and more selective BTK degrader in an ongoing Phase 1a/1b clinical trial...This trial aims to establish lisaftoclax plus acalabrutinib as a potential alternative to venetoclax-based BTKi combination..."

IO biomarker • Acute Myelogenous Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2L1 • TP53

EPCORE DLBCL-3: Subcutaneous Epcoritamab With or Without Lenalidomide as First Line Therapy for Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=111 | Active, not recruiting | Sponsor: Genmab | Recruiting ➔ Active, not recruiting | N=180 ➔ 111

Enrollment change • Enrollment closed • Monotherapy • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Diagnosis and Management of Waldenstrom's Macroglobulinemia (ICML 2025) - P2 | "New or emerging options for patients progressing on c-BTKi include pirtobrutinib, BGB-16673, venetoclax, and sonrotoclax...CXCR4 antagonists such as plerixafor or ulocuplumab can sensitize CXCR4Mut-expressing WM cells to ibrutinib [22-24]...6 BTK Mutations BTKCys481 is the binding site for covalent BTK inhibitors (cBTK-i), including ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib and tirabrutinib...For symptomatic treatment-naïve patients, chemoimmunotherapy with bendamustine and rituximab (Benda-R), dexamethasone, rituximab, and cyclophosphamide (DRC), as well as cBTK-i can be considered...Additional options in second or later relapse include re-use of chemotherapy if a response lasted for > 3 years, alternative chemoimmunotherapy, nucleoside analogs, or everolimus [38]...Zanubrutinib in combination with ixazomib and dexamethasone (ZID) is being investigated in a study in China (NCT04463953) and has shown high levels of response activity and good..."

IO biomarker • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Waldenstrom Macroglobulinemia • BCLAF1 • CXCL12 • FOXO3 • IL10 • IL6 • IRAK4 • MYD88 • PLCG2 • SYK • TNFAIP3 • TRAF3IP2

Real-world outcomes of patients with aggressive B-cell lymphoma treated with epcoritamab or glofitamab. (PubMed, Blood) - "Baseline undetectable levels of CD20 was associated with poor outcomes. These results demonstrate the activity of BsAbs in R/R DLBCL and underscore the importance of target antigen expression."

IO biomarker • Journal • Real-world evidence • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CD20

CLL12 - An ALLG phase II trial of venetoclax treatment with epcoritamab in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (ANZCTR) - P2 | N=100 | Not yet recruiting | Sponsor: Australasian Leukaemia and Lymphoma Group

New P2 trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

EPCORE NHL-5: A Study to Evaluate Adverse Events and Change in Disease Activity of Subcutaneous (SC) Epcoritamab in Combination With Oral and Intravenous Anti-Neoplastic Agents in Adult Participants With Non-Hodgkin Lymphoma (clinicaltrials.gov) - P2 | N=565 | Recruiting | Sponsor: Genmab | Phase classification: P1/2 ➔ P2

Adverse events • Phase classification • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • CCND1 • CD20

Marginal Zone Lymphoma: Treatment Update With a Focus on Systemic Approaches (ICML 2025) - P2, P3 | "Amongst 454 enrolled patients and with a median follow up time of over 7 years, the combination of rituximab plus chlorambucil had superior EFS (5-year EFS 68% vs. 50%) but no difference in overall survival which was excellent at 90% [17]. Other approaches added bendamustine to rituximab...Initial trials with the first-in-class covalent BTKi inhibitor, ibrutinib, were promising...The second generation covalent BTKi zanubrutinib and acalabrutinib have also been evaluated in RR MZL, with zanubrutinib receiving regulatory approval in the United States and the European Union...Unfortunately, the first-in-class PI3Kδ inhibitor, idelalisib, was associated with significant toxicities, including infection and immune-mediated complications...In MZL, there is a recent publication of parsaclisib with intriguing findings [29]...ZUMA-5 is a multicenter Phase 2 trial of axicabtegene ciloleucel (axi-cel) conducted in patients with both FL and MZL [30]...Several CD20xCD3 BsAbs,..."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Extranodal Marginal Zone Lymphoma • Follicular Lymphoma • Hairy Cell Leukemia • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Marginal Zone Lymphoma • Nodal Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Splenic Marginal Zone Lymphoma • CD5 • CRBN • MME • MYD88 • PIK3CD

A Phase 2 Study of Epcoritamab, Zanubrutinib, and Rituximab (EZR) for Treatment of Relapsed or Refractory Follicular Lymphoma or Marginal Zone Lymphoma (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Reid Merryman, MD | N=24 ➔ 45 | Trial completion date: Mar 2029 ➔ Mar 2030 | Trial primary completion date: Mar 2027 ➔ Mar 2028

Enrollment change • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Follicular Lymphoma: Current Therapeutic Landscape and Future Prospects (ICML 2025) - P3 | "The ability of maintenance rituximab, obinutuzumab induction, or bendamustine-based induction to lower early progression rates without affecting OS or HT rate [10, 12, 18] suggests that not all POD24 cases are equal, with a subset remaining resistant to current treatments...Since 2021, three CAR-T constructs—axicabtagene-ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel)—and three CD3 × CD20 BsAbs—mosunetuzumab, epcoritamab, and odronextamab—have gained regulatory approval in Europe and/or US as options for third line and later...Loncastuximab tesirine (CD19-directed ADC) shows promising activity in 2L+ R/R FL (CR 67%, manageable toxicity in a small Phase 2 cohort) [40]. Adding tafasitamab, an anti-CD19 antibody, to R2 in R/R FL patients improved PFS by 57% in the inMIND trial after a median follow-up of 14 months [41]...However, the ROSEWOOD trial showed obinutuzumab-zanubrutinib was superior to Obinutuzumab alone..."

IO biomarker • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • EZH2 • IGH

Subcutaneous epcoritamab monotherapy in Japanese patients with relapsed or refractory follicular lymphoma: primary results of the EPCORE NHL-3 trial. (PubMed, Leuk Lymphoma) - P1/2 | "Safety was manageable; cytokine release syndrome events had predictable timing and were mostly low grade, and no fatal treatment-emergent adverse events occurred. These results support epcoritamab as a new treatment option for Japanese patients with R/R FL.Clinical trial registration numbers: NCT04542824; JapicCTI-205408; jRCT2080225312."

Journal • Monotherapy • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

T-Cell Redirecting Strategies in Large B-Cell Lymphoma and Follicular Lymphoma (ICML 2025) - "The randomized STARGLO trial compared the combination of glofitamab with gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx, meeting its primary endpoint of OS in favor of the experimental arm (HR 0.62 [95% CI 0.43–0.88])...Other treatment options to consider in this R/R patient population are tafasitamab/lenalidomide [107], loncastuximab tesirine [108] and rituximab-bendamustine-polatuzumab [109], amongst others...Three CAR-T constructs are available based on Phase 2, single-arm trials, namely ZUMA-5 (axi-cel), ELARA (tisa-cel), and TRANSCEND-FL (liso-cel)...Mosunetuzumab, epcoritamab and odronextamab received regulatory approval (U.S...She started treatment with a bispecific antibody, aiming to carry out her first imaging assessment after three cycles. Permission to Reproduce Material From Other Sources The author has nothing to report."

IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • CD19

NEW TRENDS IN LYMPHOMA TREATMENT IN WESTERN COUNTRIES (ICML 2025) - "Second-line CAR T-cells have shown a remarkable superiority when compared to autologous stem cell transplant (ASCT) in DLBCL patients failing frontline approach (not achieving a complete response or relapsing within one year since the end of induction), which concretizes in a median event-free survival gain of at least 8 months for both axicabtagene ciloleucel and lisocabtagene maraleucel...Longer follow-up is also available for glofitamab and epcoritamab in DLBCL: for both it can be demonstrated that a 55%–64% of patients are still in CR at 24 months, and that among patients who obtained a CR at the end or during treatment (depending on the agent used) the 2-year overall survival largely exceeds 70%. Mosunetuzumab in follicular lymphoma has yielded a progression-free survival rate of 38% at 4 years, with no significant differences observed between patients progressing within 24 months since frontline treatment (POD24) and non-POD24 ones. The TRIANGLE trial has shown..."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • JAK1

Epcoritamab and Rituximab for First-line Follicular Lymphoma (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Reid Merryman, MD | Active, not recruiting ➔ Recruiting | N=35 ➔ 100 | Trial completion date: Feb 2029 ➔ Feb 2030 | Trial primary completion date: Feb 2027 ➔ Feb 2028

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

First-Line Rituximab Plus Epcoritamab May Yield High CMR Rate in FL (Hematology Advisor) - P2 | N=35 | NCT05783609 | "Among patients with follicular lymphoma (FL) with a high tumor burden, first-line rituximab plus epcoritamab may yield a high rate of complete metabolic responses (CMRs), according to research presented at the 2025 ICML Congress. The study’s findings warrant further study in an expansion cohort, the authors added...Overall, at data cut-off in January 2025, 31 of a target 35 patients had been enrolled to this study...The median follow-up was 6 months. Analysis showed that, among 25 patients with an evaluable response, 92% of patients had a CMR, with an overall response rate of 100%. In the full cohort, 48% of patients had cytokine release syndrome (all grade 1 or 2)...No relapses had been noted at data cut-off, leading to an estimated 6-month progression-free response rate of 100%....The most common adverse events other than cytokine release syndrome included fatigue (39%), injection site reactions (35%) and infections (19%)."

Cytokine release syndrome • P2 data • Follicular Lymphoma

MATCHING-ADJUSTED INDIRECT COMPARISON OF EPCORITAMAB WITH RITUXIMAB + LENALIDOMIDE VERSUS LISOCABTAGENE MARALEUCEL IN SECOND-LINE FOLLICULAR LYMPHOMA (ICML 2025) - P1/2, P2 | "These findings suggest that treatment with fixed-duration epcor + R2 in 2L FL offers comparable response rates and survival outcomes to liso-cel. Despite the limitations of the study, the findings emphasize the therapeutic potential of off-the-shelf epcor + R2 in 2L FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Heavily Pretreated Refractory Diffuse Large B-Cell Lymphoma Successfully Treated with Epcoritamab: Case Report. (PubMed, Case Rep Oncol) - "He then received dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) followed by high-dose methotrexate and initially responded but relapsed several months later. As the patient was not a candidate for transplant, subsequent treatment rounds included rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) and CD19 CAR T-cell therapy; tafasitamab-cxix and lenalidomide; and polatuzumab vedotin plus bendamustine and rituximab (pola-BR)...Within approximately 1 month, he could resume treatment, achieving a Deauville score of 1 approximately 3 months after beginning epcoritamab, and continues follow-up nearly 2 years later. T-cell engager therapies, such as epcoritamab, can play a role in managing patients with refractory DLBCL, including those refractory to CAR T-cell therapy."

Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • BCL6 • CD20

EPCORITAMAB + R-ICE IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA ELIGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANTATION: EPCORE NHL-2 (ICML 2025) - P1/2 | "Introduction: Approximately 50% of patients (pts) with LBCL are refractory to salvage chemoimmunotherapy (CIT) like rituximab, ifosfamide, carboplatin, and etoposide (R-ICE). Epcor + R-ICE demonstrated high CR rates in pts with R/R DLBCL eligible for ASCT, most of whom were high risk, having progressed < 12 mo of 1L tx. Safety was manageable, with no discontinuations due to AEs. These results demonstrate that epcor, when combined with CIT, may optimize salvage tx, increasing the proportion of pts proceeding to ASCT compared with historical rates, providing a greater chance of a cure."

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

RITUXIMAB AND EPCORITAMAB AS FIRST-LINE THERAPY FOR PATIENTS WITH HIGH-TUMOR BURDEN FOLLICULAR LYMPHOMA: FIRST RESULTS OF A MULTICENTER PHASE II TRIAL (ICML 2025) - P2 | "R+epco achieves high CMR rates in patients with high tumor burden FL, and debulking therapy with R may lower the risk of grade 2+ CRS. Based on these encouraging results, a 65-pt expansion cohort (total n = 100) is planned. Response and safety data for additional pts will be reported at the meeting."

Clinical • P2 data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

A Cost-Effectiveness Analysis of Diffuse Large B-Cell Lymphoma Treatment Pathways in the United States. (PubMed, MDM Policy Pract) - "Simulated patients received 2L axi-cel followed by 3L treatments, which were compared with treatment sequences of 2L intended autologous stem cell transplant (ASCT), polatuzumab vedotin with bendamustine and rituximab (Pola-BR), tafasitamab with lenalidomide (tafa-len), or rituximab with gemcitabine and oxaliplatin (R-GemOx), all of which were followed by 3L treatments (salvage chemotherapy, BsAbs, or axi-cel). In addition, axi-cel was compared directly with glofitamab and epcoritamab in 3L...The findings of the study suggest that although other treatments were cost-effective at lower thresholds, axi-cel is a cost-effective treatment option in 2L/3L settings in the United States. This study investigated whether axicabtagene ciloleucel (axi-cel) is cost-effective in second-line (2L) and third-line (3L) treatment sequences in the current relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treatment paradigm.Using a novel treatment sequencing model, axi-cel..."

HEOR • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

MATCHING-ADJUSTED INDIRECT COMPARISON OF EPCORITAMAB WITH RITUXIMAB + LENALIDOMIDE VS TAFASITAMAB WITH RITUXIMAB + LENALIDOMIDE IN SECOND-LINE+ FOLLICULAR LYMPHOMA (EHA 2025) - P1/2, P3 | "Findings from this MAIC highlight the potential of epcor + R2 to deliver improved ORR, CR, and PFS compared with tafasitamab + R2 in 2L+ FL."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

EPCORITAMAB PLUS LENALIDOMIDE AND RITUXIMAB ACHIEVES HIGH RESPONSE RATES AND SURVIVAL BENEFITS COMPARED WITH USUAL CARE IN RELAPSED/REFRACTORY FOLLICULAR LYMPHOMA (ICML 2025) - P1/2 | " Data included 111 epcoritamab+R2 pts and 380 usual care pts (47 R2; 333 CIT, most common bendamustine-based [65%] and CHOP-based [17%]). This study suggests epcoritamab+R2 may deliver significantly more frequent and durable responses, as well as survival benefits, versus usual care in real-world clinical practice in R/R FL. These results underscore the potential of epcoritamab+R2 as a preferred chemotherapy-free option for pts with R/R FL."

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CD20

EPCORITAMAB PLUS BENDAMUSTINE + RITUXIMAB FOR FIRST-LINE TREATMENT OF FOLLICULAR LYMPHOMA: CLINICAL AND TRANSLATIONAL RESULTS FROM EPCORE NHL-2 ARM 3 (ICML 2025) - P1/2 | "Fixed-duration epcor+BR showed deep, durable responses in 1L FL, with nearly all pts achieving CR regardless of BL BD status, and most complete responders remained in CR at 30 mo. The safety profile was manageable, with no ICANS events and only low-grade, reversible CRS. High clinical responses were observed despite reduction of CD4+ T cells and modest elevation of CD8+ T cells."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD4 • CD8

DURABLE EFFICACY WITH FIXED-DURATION EPCORITAMAB + POLATUZUMAB, VEDOTIN, RITUXIMAB, CYCLOPHOSPHAMIDE, DOXORUBICIN, AND PREDNISONE (POLA-R-CHP) FOR 1L DLBCL (EPCORE NHL-5) (ICML 2025) - P1/2 | "Introduction: First-line (1L) standard of care for diffuse large B-cell lymphoma (DLBCL) is R plus C, H, vincristine, and P (R-CHOP), and it continues to evolve with pola-R-CHP showing higher complete response rates (CRR) of 78% and longer progression-free survival than R-CHOP (Tilly 2022), However, additional therapies are needed to further improve cure rates for 1L patients (pts). Fixed-duration epcor + pola-R-CHP with follow-up of 16.1 mos in pts with newly diagnosed DLBCL continues to show high ORR and CRR across all subgroups with no new safety signals. Data continue to support that adding epcor to 1L SOC drives deep and durable responses. CRS was low-grade with predictable timing of onset."

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

MATCH-ADJUSTED COMPARATIVE ANALYSIS OF THE EFFICACY OF EPCORITAMAB + R-miniCHOP VERSUS R-miniCHOP IN PREVIOUSLY UNTREATED DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P1/2 | "Arm 8 of the EPCORE NHL-2 phase 1b/2 trial (NCT04663347) evaluated epcor plus reduced-intensity rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-miniCHOP) and demonstrated high response rates and compelling survival benefits in pts with first-line (1L) diffuse large B-cell lymphoma (DLBCL) who may be elderly, frail, and unable to tolerate standard R-CHOP. Findings suggest that epcor with R-miniCHOP significantly increases the likelihood of achieving CR and reduces the risk of progression and mortality versus R-miniCHOP."

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