Latest news with #DLBCL
Medscape
6 hours ago
- Health
- Medscape
DLBCL: Tumor Cell Signatures Predict CAR-T Success
Traits of noncancerous cells in diffuse large B-cell lymphoma (DLBCL) tumors appear to offer insight into which patients will benefit the most from chimeric antigen receptor (CAR) T-cell therapy, researchers reported at the 18th International Conference on Malignant Lymphoma (ICML) 2025 in Lugano, Switzerland, and in a simultaneously published study in Cancer Cell . An analysis of DLBCL tumor cells led by investigators from MD Anderson Cancer Center in Houston and Washington University School of Medicine in St Louis, Missouri, identified three 'lymphoma microenvironment archetype profiles' — two that are abnormal and one that is in the normal range. The research suggests that 'diffuse large B-cell lymphoma patients who have this normal lymph node environment are those most likely to benefit from CAR T-cell therapy. This may be a very useful predictive biomarker to select patients who would really benefit from this treatment,' said discussant Stephen M. Ansell, MB ChB, PhD, chair of Hematology at Mayo Clinic, Rochester, Minnesota, at an ICML session where the findings were presented. Defining the Lymphoma 'Microenvironment' The researchers launched the study to better understand the lymphoma microenvironment, defined as 'all of the nontumor cells that define the architecture and immune state of DLBCLs,' said co-author Michael R. Green, PhD, associate professor and vice chair for Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, in an interview. 'With the introduction of T-cell engaging therapies and cellular therapies, which are currently used in the relapsed/refractory setting and are likely primarily influenced by the immune microenvironment, we saw a need to provide a comprehensive map of immune and nonimmune cells within DLBCLs,' Green said. The focus, he said, is on 'how they are assembled into reproducible microenvironment archetypes and how these relate to outcome in patients treated with cellular therapy.' Using single-nucleus multiome sequencing, researchers analyzed cells from 232 tumors and 232 control tissues. At the ICML presentation, study co-author David A. Russler-Germain, MD, PhD, instructor, Division of Oncology, Washington University School of Medicine, Siteman Cancer Center/Barnes-Jewish Hospital, St. Louis, Missouri, said three archetypes of cells were identified: FMAC archetype (37% of tumors): 'Characterized by a sparsity of T/K [T/natural killer] cells and an overrepresentation of cancer-associated fibroblasts and macrophages' (37% of tumors): 'Characterized by a sparsity of T/K [T/natural killer] cells and an overrepresentation of cancer-associated fibroblasts and macrophages' LN archetype (33% of tumors): 'Characterized by naive and memory T cells together with lymph node architecture cell types' (33% of tumors): 'Characterized by naive and memory T cells together with lymph node architecture cell types' TEX archetype (30% of tumors): 'Characterized by an abundance of CD8+ T cells with markers of exhaustion' Dramatic Differences in CAR-T Response Rates Researchers applied the data to the ZUMA-7 clinical trial, which compared CAR-T cell therapy to standard chemotherapy, and found signs that the archetypes had predictive power. Patients with the LN archetype — resembling normal lymph node architecture — had the best outcomes with CAR-T therapy, achieving 67% progression-free survival at 1 year. FMAC and TEX archetypes had much lower success rates of 43% and 35%, respectively. 'The key data related to outcome is that LN archetype patients highly benefit from CAR T, FMAC patients have a diminished benefit, but it is still significantly better than standard of care, and TEX patients have no significant benefit to CAR T compared to standard of care,' Green said. 'This is the first biological subgroup of patients shown clearly not to benefit from CAR T with underlying biology that provides direct and targetable mechanisms of resistance.' Implications for Personalized Treatment As the study noted, the introduction of CAR T-cell therapy as a second-line therapy in DLBCL 'has significantly improved outcomes and leads to durable responses beyond 2 years in > 40% of patients. Nevertheless, most patients will not have durable benefit from [CAR T], highlighting a critical need to understand factors influencing response.' According to Green, the findings suggest that CAR T-cell therapy could be tailored for each archetype. 'LN patients will likely have good outcomes with CAR T alone, whereas FMAC patients have a cold microenvironment that may benefit from 'microenvironment priming' prior to CAR T, and TEX patients may require combination of CAR T cells with other agents such as interferon gamma and checkpoint-blocking antibodies.' The study's classification system, known as LymphoMAP, is not yet available in the clinic. However, it 'will be prospectively evaluated in interventional trials using microenvironment-guided therapeutic strategies using CAR-T or bispecific antibodies as a backbone,' Green said. Moving forward, discussant Ansell said, 'there is a great opportunity look at the good outcome group and say, 'What is it about them that causes about half of those patients to subsequently progress or die and not do as well as what we would hope?' How could we make that top group, the responding group, do even better?' This research was funded by the Schweitzer Family, the MD Anderson Lymphoid Malignancies Program and the National Cancer Institute. Green is a scholar of the Leukemia and Lymphoma Society, and two authors are supported by fellowships from the Lymphoma Research Foundation.
Yahoo
4 days ago
- Business
- Yahoo
ADC Therapeutics Announces Updated Data from LOTIS-7 Clinical Trial Presented at the European Hematology Association 2025 Congress
ZYNLONTA® in combination with glofitamab (COLUMVI®) in patients with r/r DLBCL demonstrated clinically meaningful benefit with overall response rate (ORR) of 93.3% and a complete response (CR) rate of 86.7% across 30 efficacy evaluable patients 25 of 26 patients achieving CR remained in CR as of the data cut-off Initial data show the combination is generally well tolerated with a manageable safety profile Company expanding enrollment for LOTIS-7 to 100 patients at 150 µg/kg dose Company to host conference call today at 8:00 a.m. ET/2:00 p.m. CEST LAUSANNE, Switzerland, June 12, 2025 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced updated data from the LOTIS-7 Phase 1b open-label clinical trial evaluating the safety and efficacy of ZYNLONTA® in combination with the bispecific antibody glofitamab (COLUMVI®) in patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) to be presented at the European Hematology Association 2025 Congress (EHA2025) in Milan, Italy. The Company will host a conference call and webcast featuring LOTIS-7 trial principal investigator and EHA presenting author, Juan Alderuccio, MD, Clinical Site Disease Group Leader, Lymphoma Section, at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine today at 8:00 a.m. ET to discuss the results. To access the conference call, please register here. "The data seen in this study with the combination of ZYNLONTA and glofitamab has shown a manageable safety profile along with strong efficacy data from patients with relapsed or refractory DLBCL, with complete responses observed regardless of prior therapy, including CAR-T," said Mohamed Zaki, MD, PhD, Chief Medical Officer of ADC Therapeutics. "The combination of these two anti-cancer agents holds significant promise for advancing the treatment landscape and addressing unmet need in patients with these hard-to-treat lymphomas." The presentation highlights updated data as of April 14, 2025, in which r/r LBCL patients received dose levels of 120 µg/kg or 150 µg/kg of ZYNLONTA plus the bispecific antibody glofitamab, with 41 patients evaluable for safety and 30 patients evaluable for efficacy. Key highlights of the LOTIS-7 data presentation are as follows: Best overall response data among the 30 efficacy evaluable patients shows overall response rate (ORR) of 93.3% (28/30 pts) as assessed by Lugano Criteria Complete response (CR) rate of 86.7% (26/30 pts) Of these, 25/26 patients achieving CR remain in CR as of the data cut-off Median time to CR in 120 µg/kg = 80 days Median time to CR in 150 µg/kg = 42 days 12 patients converted from stable disease (SD) or partial response (PR) to CR over time (1 and 11 pts respectively) Of the 6 patients previously treated with CAR-T and undergoing response assessment, 5 achieved a CR Among the 41 safety evaluable patients, the combination was generally well tolerated with a manageable safety profile and no DLTs across dose levels Grade 3 or higher treatment emergent adverse events (TEAEs) observed in > 5% of patients included neutropenia (24.4%), anemia (9.8%), AST increased (7.3%), GGT increased (7.3%), and thrombocytopenia (7.3%) In the 150 µg/kg dose, cytokine release syndrome (CRS) (23.8%), all of which were Grade 1, and immune effector cell-associated neurotoxicity syndrome (ICANS) (4.8%), with one case of Grade 2, were observed In the 120 µg/kg dose, CRS all grades (55%), all of which were Grade 1/2 except one case of Grade 3, and ICANS (10%), with one case of Grade 1 and one case of Grade 2, were observed TEAEs leading to discontinuation included 3 each for ZYNLONTA and glofitamab There were no Grade 5 TEAEs observed "We believe these new data are differentiating and further reinforce the potential of ZYNLONTA plus the bispecific glofitamab to improve outcomes for DLBCL patients who need it most," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "This early safety and efficacy data support the ongoing expansion of this study to 100 patients at the 150 µg/kg dose of ZYNLONTA plus glofitamab. We look forward to discussing the results with Dr. Alderuccio during our conference call today in addition to the presentation of the data set across two key conferences." This data will be shared at EHA2025 during a poster presentation on June 14 at 6:30 p.m. CEST and also as an oral encore presentation at the 18th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland on Friday, June 20 at 9:00 a.m. ET. The Company plans to share additional data before the end of 2025. Conference Call InformationTo access the conference call, please register here. The participant toll-free dial-in number is 1-800-836-8184 for North America and Canada. It is recommended that you join 10 minutes before the event, though you may pre-register at any time. A live webcast of the call will be available under "Events and Presentations" in the Investors section of the ADC Therapeutics website at The archived webcast will be available for 30 days following the call. About LOTIS-7LOTIS-7 is a Phase 1b global multicenter, multi-arm study in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) including Part 1 (dose escalation) and Part 2 (dose expansion). The three dosing arms include ZYNLONTA plus polatuzumab vedotin, ZYNLONTA plus glofitamab, and ZYNLONTA plus mosunetuzumab T-cell-engaging bispecific monoclonal antibodies (BsAbs). Enrollment in LOTIS-7 includes Part 1 of the study with a 3+3 dose escalation in 3L/3L+ heavily pre-treated patients with ZYNLONTA doses starting at 90 µg/kg and then proceeding to 120 µg/kg and 150 µg/kg. Part 2 includes dose expansion in 2L/2L+ large B-cell lymphoma in the ZYNLONTA plus glofitamab arm at dose levels determined from Part 1 (120 µg/kg and 150 µg/kg of ZYNLONTA plus the approved dosing of glofitamab). Primary endpoints of the study include safety and tolerability. Secondary efficacy endpoints include ORR, DOR, CRR, PFS, RFS, and OS as well as pharmacokinetics and immunogenicity. For more information about the LOTIS-7 trial, visit (NCT04970901). About ZYNLONTA® ZYNLONTA® is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at ZYNLONTA is also being evaluated as a therapeutic option in combination studies in other B-cell malignancies and earlier lines of therapy. About ADC Therapeutics ADC Therapeutics (NYSE: ADCT) is a commercial-stage biotechnology company helping to improve the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs). The Company is advancing its proprietary ADC technology to transform the treatment paradigm for patients with hematologic malignancies and solid tumors. ADC Therapeutics' CD19-directed ADC ZYNLONTA (loncastuximab tesirine-lpyl) received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. In addition to ZYNLONTA, ADC Therapeutics has multiple ADCs in ongoing clinical and preclinical development. ADC Therapeutics is based in Lausanne (Biopôle), Switzerland and has operations in London and New Jersey. For more information, please visit and follow the Company on LinkedIn. ZYNLONTA® is a registered trademark of ADC Therapeutics SA. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements regarding the potential of ZYNLONTA® in combination with the bispecific antibody glofitamab, including the reproducibility and durability of any favorable results initially seen in patients dosed to date, and the Company's research, development and regulatory plans, including the timing and results of clinical trials and the timing and outcome of regulatory submissions. In some cases you can identify forward-looking statements by terminology such as "may", "will", "should", "would", "expect", "intend", "plan", "anticipate", "believe", "estimate", "predict", "potential", "seem", "seek", "future", "continue", or "appear" or the negative of these terms or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: whether future LOTIS-7 clinical trial results will be consistent with or different from the LOTIS-7 data presented at EHA and ICML and future compendia and regulatory strategy and opportunity; the expected cash runway into mid-2026 the Company's ability to grow ZYNLONTA® revenue in the United States; the ability of our partners to commercialize ZYNLONTA® in foreign markets, the timing and amount of future revenue and payments to us from such partnerships and their ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions; the timing and results of the Company's or its partners' research and development projects or clinical trials including LOTIS 5 and 7, as well as early research in certain solid tumors with different targets, linkers and payloads; the timing and results of investigator-initiated trials including those studying FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; the timing and outcome of regulatory submissions for the Company's products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company's indebtedness, including Healthcare Royalty Management and Blue Owl and Oaktree facilities, and the restrictions imposed on the Company's activities by such indebtedness, the ability to comply with the terms of the various agreements and repay such indebtedness and the significant cash required to service such indebtedness; and the Company's ability to obtain financial and other resources for its research, development, clinical, and commercial activities. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K and in the Company's other periodic and current reports and filings with the U.S. Securities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any future results, performance, achievements or prospects expressed in or implied by such forward-looking statements. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this document. CONTACTS:Investor RelationsMarcy GrahamADC 650-667-6450 Media RelationsNicole RileyADC 862-926-9040 View original content to download multimedia: SOURCE ADC Therapeutics SA Errore nel recupero dei dati Effettua l'accesso per consultare il tuo portafoglio Errore nel recupero dei dati Errore nel recupero dei dati Errore nel recupero dei dati Errore nel recupero dei dati
Medscape
5 days ago
- Health
- Medscape
Pola-R-GemOx Boosts Survival in R/R DLBCL
MILAN — Combining polatuzumab vedotin (Pola) with rituximab, gemcitabine, and oxaliplatin (R-GemOx) significantly improves survival outcomes in patients with transplant-ineligible, relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), according to new data from the phase 3 POLARGO trial. Presented by Matthew Matasar, MD, chief of the division of blood disorders at Rutgers Cancer Institute, New Brunswick, New Jersey, here at the European Hematology Association (EHA) 2025 Annual Meeting, the study showed a 40% reduction in the relative risk of death with Pola-R-GemOx versus R-GemOx alone. "These are the gems of the congress," said Martin Dreyling, MD, scientific program committee chair for EHA2025, who presided over the session, describing this and similar studies as potentially practice-changing. Improved OS and PFS Matthew Matasar, MD The global trial enrolled 270 patients with R/R DLBCL who were ineligible for autologous stem cell transplant, had received at least one prior line of therapy, and had not previously been treated with Pola. Of those, 255 were randomized 1:1 to receive Pola-R-GemOx or R-GemOx every 21 days for up to 8 cycles. Patients were stratified by age (≤70 vs >70 years), prior lines of therapy (1 vs ≥2), and response to the most recent treatment (relapsed vs refractory). Baseline characteristics were well-balanced between groups; two thirds were treated in the second-line setting and most had refractory disease. At a median follow-up of 24.6 months, the primary endpoint was met: median overall survival (OS) was 19.5 months with Pola-R-GemOx versus 12.5 months with R-GemOx (hazard ratio [HR], 0.60; 95% CI, 0.43-0.83; P = .0017). Two-year OS was 44.0% versus 33.2%, respectively. Progression-free survival (PFS) also significantly improved at a median follow-up of 18.7 months (HR, 0.37; 95% CI, 0.27-0.51; P = .0001), increasing from 2.7 months to 7.4 months. The 12-month PFS was 36.6% for Pola-R-GemOx and 17.9% for R-GemOx. Response rates were nearly double in the experimental group. The overall response rate (ORR) was 52.7% versus 24.6% and the complete response rate was 40.3% versus 19.0%, respectively, as assessed by an independent review committee. Subgroup and Safety Analyses The OS benefit was consistent across subgroups, including those with and without bulky disease, and among both primary refractory and non-refractory patients. Notably, survival benefit was seen in both activated B-cell (ABC) and germinal center B-cell (GCB) subtypes — contrary to prior findings from the POLARIX trial, which had suggested preferential benefit in the ABC subtype. Matasar emphasized the robustness of the results, noting that patients receiving R-GemOx underwent more subsequent lines of therapy, ruling out confounding by post-progression treatment access. However, the enhanced efficacy came with increased toxicity. Patients in the Pola-R-GemOx group received a median of 7.5 cycles versus 4 cycles in the R-GemOx group. Treatment discontinuations due to adverse events (AEs) were more common with Pola-R-GemOx (23.4% vs 8.0%). Grade 3-4 AE rates were similar (57.0% vs 58.4%), though thrombocytopenia and infections were more frequent in the experimental group. Infections were the leading cause of grade 5 AEs, including 10 COVID-related deaths (seven during treatment, three after completion). "It's worth remembering that the study was conducted during the peak of the COVID-19 pandemic," Matasar noted. Peripheral neuropathy, an expected AE due to overlapping neurotoxicities of Pola and oxaliplatin, was observed in 57.0% of patients receiving Pola-R-GemOx versus 28.8% with R-GemOx. Most cases were grade 1, but 3.9% of patients in the experimental group had grade 3 events. "Peripheral neuropathy was not permanent in all patients, approximately half of the patients did experience improvement in neuropathy by the time of study closure, and approximately one third of patients had complete resolution," Matasar reported. A Role in Bridging Therapy? Frank Leebeek, MD, PhD Commenting to Medscape Medical News, Frank Leebeek, MD, PhD, chair of hematology at Erasmus University, Rotterdam, Netherlands, who was not involved in the trial, said: "This is very important. Prognosis remains poor for patients with R/R DLBCL who cannot receive or are ineligible for transplant." He welcomed the new option in the arsenal of treatments for this disease. Concluding his presentation, Matasar stressed the importance of having different tools. "Some patients will be appropriate for CAR-T, some for bispecific antibodies, some will have access to neither and benefit from ADC destination therapy. Pola-R-GemOx represents an alternative treatment option," he said. Leebeek noted that Pola-R-GemOx may serve as a bridge therapy to CAR-T because it does not deplete the T-cell population. "Achieving complete remission after relapse is challenging," he said, "and other regimens can impair the T-cell pool, while this one doesn't." The study was funded by F. Hoffmann-La Roche. Matasar has disclosed financial relationships with ADC Therapeutics, AbbVie, Arvinas, AstraZeneca, Bayer, BMS, Genmab, Ipsen, J&J, Kite, Novartis, Regeneron, Roche, and Pfizer, and research support from Allogene, Arvinas, Bayer, Cellectis, Genentech, J&J, Pfizer, Pharmacyclics, Regeneron, and Roche. He has reported serving as a consultant for AbbVie, Allogene, Arvinas, Bayer, BMS, Genentech, Genmab, Kite, Novartis, Pfizer, and Roche, and being a current equity holder of Merck. Leebeek has reported no relevant financial relationships.
Associated Press
5 days ago
- Health
- Associated Press
Genmab Announces Epcoritamab Investigational Combination Therapy Demonstrates High Response Rates in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Eligible for Autologous Stem Cell Transplantation (ASCT)
COPENHAGEN, Denmark--(BUSINESS WIRE)--Jun 15, 2025-- Genmab A/S(Nasdaq: GMAB) today announced new results from the Phase 1b/2 EPCORE ® NHL-2 trial Arm 10 (NCT04663347), evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in adult patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are eligible for autologous stem cell transplantation (ASCT). Results demonstrated an overall response rate (ORR) of 87 percent, a complete response (CR) rate of 65 percent and a partial response (PR) of 23 percent. The majority of patients (65 percent) proceeded to ASCT. At six months, an estimated 81 percent of responses were ongoing, 74 percent of patients were progression free, and 100 percent of patients were alive. These results were shared today during an oral presentation at the 30 th European Hematology Association (EHA) 2025 Congress. The safety profile of this combination therapy showed cytokine release syndrome (CRS) being low grade and no discontinuations due to treatment-emergent adverse events (TEAEs). The most common TEAEs were neutropenia (74 percent), anemia (68 percent), and thrombocytopenia (68 percent). CRS occurred in 52 percent; all were low grade (1/2) and resolved. One patient had immune effector cell-associated neurotoxicity syndrome (ICANS; grade 1), which resolved. No clinical tumor lysis syndrome was observed. Infections occurred in 18 patients (58 percent); five (16 percent) had serious infections. 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,' said Raul Cordoba, MD, PhD, Head of the Lymphoma Unit at the Fundacion Jimenez Diaz University Hospital, Madrid, Spain. '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.' Among patients in the study who progressed within 12 months after first-line treatment (n=20), epcoritamab in combination with R-ICE demonstrated an 85 percent ORR and 55 percent CR. Patients in the study who progressed after 12 months from first-line therapy experienced a 91 percent ORR and 82 percent CR. Additionally, patients with one prior line of therapy experienced an 88 percent ORR and 68 percent CR, and patients who were treated with more than one prior line of therapy experienced an 83 percent ORR and 50 percent 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. 'Our 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.' Use of epcoritamab + R-ICE in patients with R/R DLBCL eligible for ASCT is not approved and the safety and efficacy of epcoritamab for use as a combination therapy in DLBCL have not been established. About Diffuse Large B-Cell Lymphoma DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases. In the U.S., there are approximately 25,000 new cases of DLBCL diagnosed each year. 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. 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. About the EPCORE ® NHL-2 Trial EPCORE NHL-2 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's 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 endpoint was overall response rate (ORR) based on best overall response per Lugano criteria. MRD negativity was assessed as a secondary endpoint. Arm 10 of the EPCORE NHL-2 study enrolled 31 patients with R/R DLBCL, who were eligible for R-ICE and ASCT, and had received ≥1 prior line of treatment. At the time of data cutoff (December 18, 2024), median follow-up was 11 months (range, 6−15). Among the 31 patients treated with epcoritamab 48 mg + R-ICE, 61 percent were Ann Arbor stage III/IV, 42 percent had bulky disease ≥7 cm, 81 percent had one prior LOT (range, 1−3), and 65 percent had progressed within 12 months of first-line treatment. More information on this trial can be found at (NCT: 04663347). 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. i 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 several territories. Where approved, epcoritamab is available as a readily accessible therapy without the need for reducing tumor burden ('debulking'). Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies will 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 R/R FL indication and additional approvals for the R/R 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 five ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy ( NCT04628494 ), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL ( NCT05578976 ), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL ( NCT05409066 ), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL ( NCT06191744 ), and a trial evaluating epcoritamab in combination with R2 compared to chemotherapy infusion in patients with R/R DLBCL ( NCT06508658 ). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit for more information. 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: 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: 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 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 is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab's vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO ® ) antibody medicines. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit 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 the risk factors included in Genmab's most recent Annual Report on Form 20-F and other filingswith the U.S. Securities and Exchange Commission (SEC), which are available 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/ View source version on CONTACT: David Freundel, Senior Director, Global R&D & Portfolio Communications T: +1 609 613 0504; E:[email protected] Carlsen, Vice President, Head of Investor Relations T: +45 3377 9558; E:[email protected] KEYWORD: DENMARK EUROPE INDUSTRY KEYWORD: SCIENCE OTHER SCIENCE BIOTECHNOLOGY RESEARCH PHARMACEUTICAL ONCOLOGY HEALTH CLINICAL TRIALS SOURCE: Genmab Copyright Business Wire 2025. PUB: 06/15/2025 05:00 AM/DISC: 06/15/2025 04:58 AM
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Genmab Announces Epcoritamab Investigational Combination Therapy Demonstrates High Response Rates in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) Eligible for Autologous Stem Cell Transplantation (ASCT)
Media ReleaseCOPENHAGEN, Denmark; June 15, 2025 Results from the EPCORE® NHL-2 trial show investigational treatment with epcoritamab in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) led to an overall response rate (ORR) of 87 percent and a complete response (CR) rate of 65 percent in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) Data further demonstrates the potential of epcoritamab in combination with salvage chemoimmunotherapy to increase the proportion of patients to qualify for Autologous Stem Cell Transplantation (ASCT) Data was presented during an oral session at the 30th European Hematology Association (EHA) Congress Genmab A/S (Nasdaq: GMAB) today announced new results from the Phase 1b/2 EPCORE® NHL-2 trial Arm 10 (NCT04663347), evaluating epcoritamab, a T-cell engaging bispecific antibody administered subcutaneously, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in adult patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who are eligible for autologous stem cell transplantation (ASCT). Results demonstrated an overall response rate (ORR) of 87 percent, a complete response (CR) rate of 65 percent and a partial response (PR) of 23 percent. The majority of patients (65 percent) proceeded to ASCT. At six months, an estimated 81 percent of responses were ongoing, 74 percent of patients were progression free, and 100 percent of patients were alive. These results were shared today during an oral presentation at the 30th European Hematology Association (EHA) 2025 Congress. The safety profile of this combination therapy showed cytokine release syndrome (CRS) being low grade and no discontinuations due to treatment-emergent adverse events (TEAEs). The most common TEAEs were neutropenia (74 percent), anemia (68 percent), and thrombocytopenia (68 percent). CRS occurred in 52 percent; all were low grade (1/2) and resolved. One patient had immune effector cell-associated neurotoxicity syndrome (ICANS; grade 1), which resolved. No clinical tumor lysis syndrome was observed. Infections occurred in 18 patients (58 percent); five (16 percent) had serious infections. 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,' said Raul Cordoba, MD, PhD, Head of the Lymphoma Unit at the Fundacion Jimenez Diaz University Hospital, Madrid, Spain. '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." Among patients in the study who progressed within 12 months after first-line treatment (n=20), epcoritamab in combination with R-ICE demonstrated an 85 percent ORR and 55 percent CR. Patients in the study who progressed after 12 months from first-line therapy experienced a 91 percent ORR and 82 percent CR. Additionally, patients with one prior line of therapy experienced an 88 percent ORR and 68 percent CR, and patients who were treated with more than one prior line of therapy experienced an 83 percent ORR and 50 percent 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. 'Our 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." Use of epcoritamab + R-ICE in patients with R/R DLBCL eligible for ASCT is not approved and the safety and efficacy of epcoritamab for use as a combination therapy in DLBCL have not been established. About Diffuse Large B-Cell LymphomaDLBCL is the most common type of non-Hodgkin's lymphoma (NHL) worldwide, accounting for approximately 25-30 percent of all NHL cases. In the U.S., there are approximately 25,000 new cases of DLBCL diagnosed each year. 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. 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. About the EPCORE® NHL-2 Trial EPCORE NHL-2 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's 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 endpoint was overall response rate (ORR) based on best overall response per Lugano criteria. MRD negativity was assessed as a secondary endpoint. Arm 10 of the EPCORE NHL-2 study enrolled 31 patients with R/R DLBCL, who were eligible for R-ICE and ASCT, and had received ≥1 prior line of treatment. At the time of data cutoff (December 18, 2024), median follow-up was 11 months (range, 6−15). Among the 31 patients treated with epcoritamab 48 mg + R-ICE, 61 percent were Ann Arbor stage III/IV, 42 percent had bulky disease ≥7 cm, 81 percent had one prior LOT (range, 1−3), and 65 percent had progressed within 12 months of first-line treatment. More information on this trial can be found at (NCT: 04663347). 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.i 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 several territories. Where approved, epcoritamab is available as a readily accessible therapy without the need for reducing tumor burden ('debulking'). Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies will 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 R/R FL indication and additional approvals for the R/R 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 five ongoing Phase 3, open-label, randomized trials including a trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL compared to investigators choice chemotherapy (NCT04628494), a trial evaluating epcoritamab in combination with R-CHOP in adult patients with newly diagnosed DLBCL (NCT05578976), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) in patients with R/R FL (NCT05409066), a trial evaluating epcoritamab in combination with rituximab and lenalidomide (R2) compared to chemoimmunotherapy in patients with previously untreated FL (NCT06191744), and a trial evaluating epcoritamab in combination with R2 compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit for more information. About GenmabGenmab is an international biotechnology company with a core purpose of guiding its unstoppable team to strive toward improving the lives of patients with innovative and differentiated antibody therapeutics. For 25 years, its passionate, innovative and collaborative team has invented next-generation antibody technology platforms and leveraged translational, quantitative and data sciences, resulting in a proprietary pipeline including bispecific T-cell engagers, antibody-drug conjugates, next-generation immune checkpoint modulators and effector function-enhanced antibodies. By 2030, Genmab's vision is to transform the lives of people with cancer and other serious diseases with knock-your-socks-off (KYSO®) antibody medicines. Established in 1999, Genmab is headquartered in Copenhagen, Denmark, with international presence across North America, Europe and Asia Pacific. For more information, please visit and follow us on LinkedIn and X. Contact: David Freundel, Senior Director, Global R&D & Portfolio CommunicationsT: +1 609 613 0504; E: dafr@ Andrew Carlsen, Vice President, Head of Investor RelationsT: +45 3377 9558; E: acn@ 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 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 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/ Media Release no. i13CVR no. 2102 3884LEI Code 529900MTJPDPE4MHJ122 Genmab A/SCarl Jacobsens Vej 302500 ValbyDenmarkAttachment 15062025_MRi13_EHA 2025 EPCORE NHL-2
