Two Data Analyses From Clinical Trials Show Epcoritamab (DuoBody® CD3xCD20) Induces Durable Complete Reponses As Monotherapy and Combination Treatment in Patients With Diffuse Large B-Cell Lymphoma
AbbVie (ABBV) announced new results from two ongoing clinical trials of epcoritamab in patients with diffuse large B-cell lymphoma (DLBCL). The Phase 1b/2 EPCORE NHL-2 trial showed 100% overall response rate and 87% complete response rate in untreated high-risk DLBCL patients when combined with R-CHOP therapy. Among complete responders, 83% remained in remission after two years.
The Phase 2 EPCORE NHL-1 trial's three-year follow-up, evaluating epcoritamab monotherapy in relapsed/refractory patients, demonstrated 59% overall response rate and 41% complete response rate. Among complete responders, 52% maintained response at three years, with median complete response duration of 36.1 months.
AbbVie (ABBV) ha annunciato nuovi risultati provenienti da due studi clinici in corso su epcoritamab in pazienti affetti da linfoma diffuso a grandi cellule B (DLBCL). Lo studio Fase 1b/2 EPCORE NHL-2 ha mostrato un tasso di risposta complessivo del 100% e un tasso di risposta completa dell'87% nei pazienti ad alto rischio di DLBCL non trattati, quando combinato con la terapia R-CHOP. Tra i rispondenti completi, l'83% è rimasto in remissione dopo due anni.
Il follow-up di tre anni dello studio Fase 2 EPCORE NHL-1, che valuta il trattamento con epcoritamab in monoterapia in pazienti in recidiva/rimasti refrattari, ha dimostrato un tasso di risposta complessivo del 59% e un tasso di risposta completa del 41%. Tra i rispondenti completi, il 52% ha mantenuto la risposta a tre anni, con una durata mediana della risposta completa di 36,1 mesi.
AbbVie (ABBV) anunció nuevos resultados de dos ensayos clínicos en curso de epcoritamab en pacientes con linfoma difuso de células B grandes (DLBCL). El ensayo de Fase 1b/2 EPCORE NHL-2 mostró una tasa de respuesta general del 100% y una tasa de respuesta completa del 87% en pacientes con DLBCL de alto riesgo no tratados, cuando se combina con la terapia R-CHOP. Entre los respondedores completos, el 83% se mantuvo en remisión después de dos años.
El seguimiento de tres años del ensayo de Fase 2 EPCORE NHL-1, que evalúa la monoterapia con epcoritamab en pacientes en recaída/refractarios, demostró una tasa de respuesta general del 59% y una tasa de respuesta completa del 41%. Entre los respondedores completos, el 52% mantuvo la respuesta a los tres años, con una duración media de la respuesta completa de 36,1 meses.
AbbVie (ABBV)는 미만성 거대 B세포 림프종(DLBCL) 환자에서 epcoritamab에 대한 진행 중인 두 임상 시험의 새로운 결과를 발표했습니다. 1b/2상 EPCORE NHL-2 시험에서 R-CHOP 요법과 병용했을 때 치료를 받지 않은 고위험 DLBCL 환자에서 전체 응답률이 100% 및 완전 응답률이 87%로 나타났습니다. 완전 응답자 중 83%는 2년 후에도 완전히 REMISSION을 유지했습니다.
재발/내성과 같은 환자에서 epcoritamab 단독요법을 평가하는 2상 EPCORE NHL-1 시험의 3년 추적 조사에서는 59%의 전체 응답률과 41%의 완전 응답률이 나타났습니다. 완전 응답자 중 52%는 3년 후에도 반응을 유지했으며, 완전 반응의 중간 지속 기간은 36.1개월이었습니다.
AbbVie (ABBV) a annoncé de nouveaux résultats de deux essais cliniques en cours sur l'épcoritamab chez des patients atteints de lymphome diffus à grandes cellules B (DLBCL). L'essai de phase 1b/2 EPCORE NHL-2 a montré un taux de réponse global de 100 % et un taux de réponse complète de 87 % chez les patients DLBCL à haut risque non traités lorsqu'il est associé à la thérapie R-CHOP. Parmi les répondants complets, 83 % sont restés en rémission après deux ans.
Le suivi de trois ans de l'essai de phase 2 EPCORE NHL-1, évaluant l'épcoritamab en monothérapie chez des patients en rechute/résistants, a démontré un taux de réponse global de 59 % et un taux de réponse complète de 41 %. Parmi les répondants complets, 52 % ont maintenu leur réponse après trois ans, avec une durée médiane de réponse complète de 36,1 mois.
AbbVie (ABBV) hat neue Ergebnisse aus zwei laufenden klinischen Studien zu Epcoritamab bei Patienten mit diffus großzelligem B-Zell-Lymphom (DLBCL) angekündigt. Die Phase 1b/2 Studie EPCORE NHL-2 zeigte eine Gesamtansprechrate von 100 % und eine komplette Ansprechrate von 87 % bei unbehandelten Hochrisiko-DLBCL-Patienten in Kombination mit R-CHOP-Therapie. Unter den kompletten Ansprechern blieben 83 % nach zwei Jahren in Remission.
Die dreijährige Nachuntersuchung der Phase-2-Studie EPCORE NHL-1, die Epcoritamab als Monotherapie bei rezidivierenden/refraktären Patienten bewertet, zeigte eine Gesamtansprechrate von 59 % und eine komplette Ansprechrate von 41 %. Unter den kompletten Ansprechern erhielten 52 % die Antwort nach drei Jahren, mit einer medianen Dauer der kompletten Antwort von 36,1 Monaten.
- 100% overall response rate in combination therapy trial
- 87% complete response rate in first-line treatment
- 83% two-year remission rate in complete responders
- 52% three-year response duration in monotherapy trial
- 91% of patients achieved minimal residual disease negativity in combination therapy
- 9% of patients discontinued treatment due to adverse events
- Two fatal treatment-emergent adverse events reported
- 73% of long-term patients experienced Grade 3 or higher infections
- 20 fatal treatment-emergent adverse events in monotherapy trial
- Immunoglobulin G levels decreased by ~20% after treatment initiation
Insights
The clinical trial results for epcoritamab show remarkable promise in both combination therapy and monotherapy settings. The 100% overall response rate and 87% complete response rate in previously untreated high-risk DLBCL patients, combined with an estimated 83% remission rate at two years, are particularly impressive for this difficult-to-treat population. These metrics significantly exceed historical standards for high-risk DLBCL treatment.
The durability of response in the third-line setting is equally noteworthy, with a median complete response duration of 36.1 months. The high rates of minimal residual disease negativity (91% in first-line and 45.4% in third-line) suggest deep and potentially lasting responses. The safety profile appears manageable, with primarily low-grade cytokine release syndrome that resolved in all cases.
This data strengthens ABBV's position in the competitive hematologic oncology market. With an addressable market of approximately 25,000 new DLBCL cases annually in the U.S. alone, successful expansion into first-line therapy could significantly boost epcoritamab's commercial potential. The strong efficacy data in high-risk patients could lead to broader adoption and potentially earlier treatment lines, expanding the revenue opportunity.
The positive results support ongoing Phase 3 trials and could accelerate the path to additional regulatory approvals. This could help offset some of AbbVie's revenue concerns as Humira faces biosimilar competition. The combination therapy approach with R-CHOP could also provide a competitive advantage in the increasingly crowded DLBCL market.
- Data presented at the 66th Annual Meeting and Exposition of the American Society of Hematology (ASH)
Arm 1 of the Phase 1b/2 EPCORE® NHL-2 multi-arm trial evaluates fixed-duration investigational epcoritamab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated high-risk DLBCL patients (n=46) with International Prognostic Index (IPI) scores of 3 to 5 (Abstract #581).1 Results from this arm of the study showed an overall response rate (ORR) of
DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) worldwide, accounting for approximately 25
"The results from these epcoritamab studies help provide confidence in our ongoing Phase 3 trials and highlight our commitment to advancing treatment standards for this challenging type of cancer," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "We remain dedicated to exploring epcoritamab both as a monotherapy and in combination with other therapies for earlier lines of treatment, as well as establishing it as a core therapy across B-cell malignancies."
EPCORE® NHL-2 Results in First-Line DLBCL (Abstract #581)
The EPCORE NHL-2 trial enrolled 46 evaluable patients considered to have high-risk DLBCL, identified by International Prognostic Index (IPI) scores of 3 to 5, a range associated with poor long-term outcomes. The IPI is a key tool used by oncologists to predict the prognosis of aggressive B-cell lymphomas.9 At screening,
A minimal residual disease (MRD) analysis from blood samples (n=33) showed that
The most common treatment-emergent adverse events (TEAEs) were neutropenia (
EPCORE® NHL-1 Results in Third-Line LBCL (Abstract #4480)
Three-year follow-up results from the Phase 2 EPCORE® NHL-1 trial evaluated epcoritamab monotherapy in 157 patients with R/R LBCL after two or more lines of prior therapy and showed that epcoritamab continues to deliver durable responses in challenging-to-treat patients. Additional data results include:
- The ORR was
59% , and CR was41% . Median duration of response was 20.8 months (95% CI, 13.0-32.0) and median duration of CR was 36.1 months (95% CI, 20.2 to not reached [NR]). - A MRD analysis from blood samples (n=119) showed that
45.4% of patients achieved MRD negativity, as defined by ctDNA.11
The most common TEAEs were CRS (
"More first-line treatments for diffuse large B-cell lymphoma are needed, especially for patients with aggressive disease markers that may impact the efficacy of current standard first-line therapies," said Lorenzo Falchi, M.D., Lymphoma Specialist, Department of Medicine, Memorial Sloan Kettering Cancer Center. "The durable responses observed in the study suggest significant potential for this first-line epcoritamab-based combination."
Epcoritamab (approved under the brand name EPKINLY in the
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 it includes Arms 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, 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 1 of the trial is epcoritamab plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R‑CHOP) in adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL). More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT: 04663347).
About the EPCORE® NHL-1 Trial
EPCORE® NHL-1 is an open-label, multicohort, single-arm, Phase 1/2 trial of epcoritamab in participants with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL). The trial was conducted at 88 sites across 15 countries and consisted of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. More information on this trial can be found at https://www.clinicaltrials.gov/ (NCT: 03625037).
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.12 Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies' oncology collaboration. The companies share commercial responsibilities in the
EPKINLY® (epcoritamab-bysp)
What is EPKINLY?
EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, or follicular lymphoma (FL) that has come back or that did not respond to previous treatment after receiving 2 or more treatments. EPKINLY is approved based on patient response data. Studies are ongoing to confirm the clinical benefit of EPKINLY. It is not known if EPKINLY is safe and effective in children.
Important Warnings—EPKINLY can cause serious side effects, including:
- Cytokine release syndrome (CRS), which is common during treatment with EPKINLY and can be serious or life-threatening. To help reduce your risk of CRS, you will receive EPKINLY on a step-up dosing schedule (when you receive 2 or 3 smaller step-up doses of EPKINLY before your first full dose during your first cycle of treatment), and you may also receive other medicines before and for 3 days after receiving EPKINLY. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule.
- Neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY.
People with DLBCL or high-grade B-cell lymphoma should be hospitalized for 24 hours after receiving their first full dose of EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic problems.
Tell your healthcare provider or get medical help right away if you develop a fever of 100.4°F (38°C) or higher; dizziness or lightheadedness; trouble breathing; chills; fast heartbeat; feeling anxious; headache; confusion; shaking (tremors); problems with balance and movement, such as trouble walking; trouble speaking or writing; confusion and disorientation; drowsiness, tiredness or lack of energy; muscle weakness; seizures; or memory loss. These may be symptoms of CRS or neurologic problems. If you have any symptoms that impair consciousness, do not drive or use heavy machinery or do other dangerous activities until your symptoms go away.
EPKINLY can cause other serious side effects, including:
- Infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment and treat you as needed if you develop an infection. You should receive medicines from your healthcare provider before you start treatment to help prevent infection. Tell your healthcare provider right away if you develop any symptoms of infection during treatment, including fever of 100.4°F (38°C) or higher, cough, chest pain, tiredness, shortness of breath, painful rash, sore throat, pain during urination, or feeling weak or generally unwell.
- Low blood cell counts, which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment. EPKINLY may cause low blood cell counts, including low white blood cells (neutropenia), which can increase your risk for infection; low red blood cells (anemia), which can cause tiredness and shortness of breath; and low platelets (thrombocytopenia), which can cause bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS, neurologic problems, infections, and low blood cell counts during treatment with EPKINLY. Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.
Before you receive EPKINLY, tell your healthcare provider about all your medical conditions, including if you have an infection, are pregnant or plan to become pregnant, or are breastfeeding or plan to breastfeed. If you receive EPKINLY while pregnant, it may harm your unborn baby. If you are a female who can become pregnant, your healthcare provider should do a pregnancy test before you start treatment with EPKINLY and you should use effective birth control (contraception) during treatment and for 4 months after your last dose of EPKINLY. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with EPKINLY. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.
In DLBCL or high-grade B-cell lymphoma, the most common side effects of EPKINLY include CRS, tiredness, muscle and bone pain, injection site reactions, fever, stomach-area (abdominal) pain, nausea, and diarrhea. The most common severe abnormal laboratory test results include decreased white blood cells, decreased red blood cells, and decreased platelets.
In follicular lymphoma the most common side effects of EPKINLY include injection site reactions, CRS, COVID-19, tiredness, upper respiratory tract infections, muscle and bone pain, rash, diarrhea, fever, cough, and headache. The most common severe abnormal laboratory test results include decreased white blood cells and decreased red blood cells.
These are not all of the possible side effects of EPKINLY. Call your doctor for medical advice about side effects. You are encouraged to report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at 1-855-4GENMAB (1-855-443-6622).
Please see Full Prescribing Information and Medication Guide, including Important Warnings.
Globally, prescribing information varies; refer to the individual country product label for complete information.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.
AbbVie Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2023 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.
Disclosure: Dr. Falchi has financial interests related to AbbVie and Genmab.
1 Falchi, et al. Fixed-Duration Epcoritamab + R-CHOP Induces High Complete Response Rates in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma With High-Risk Features: Long-Term Results from the Epcore NHL-2 Trial. Abstract retrieved from ASH Annual Meeting & Exposition Database. 2024.
2 Vose, et al. 3-Year Update from the Epcore NHL-1 Trial: Epcoritamab Leads to Deep and Durable Responses in Relapsed or Refractory Large B-Cell Lymphoma. Abstract retrieved from ASH Annual Meeting & Exposition Database. 2024.
3 Lymphoma Research Foundation. Diffuse Large B-Cell Lymphoma. Accessed November 2024. https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/dlbcl/
4 Padala, et al. Diffuse Large B-Cell Lymphoma. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. 2023 Apr 24.
5 Leukemia and Lymphoma Society. Diffuse Large B-Cell Lymphoma (DLBCL). Accessed November 2024. https://www.lls.org/research/diffuse-large-b-cell-lymphoma-dlbcl
6 Sehn, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384:842-858. doi: 10.1056/NEJMra2027612.
7 Kanas, et al. Epidemiology of Diffuse Large B-Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) in
8 Crump, et al. Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results From the International SCHOLAR-1 Study. Blood. 2017;130(16):1800-1808. doi: 10.1182/blood-2017-03-769620.
9 Maurer M. The International Prognostic Index in aggressive B-cell lymphoma. Haematologica. 2023 Nov 1;108(11):2874–2879. doi: 10.3324/haematol.2023.284070
10 Soong, et al. Evaluation of ctDNA in a phase I/II trial in relapsed or refractory large B-cell lymphoma of epcoritamab, a novel, subcutaneous CD3xCD20 bispecific T-cell–engaging antibody. Hematological Oncology. 2023; 326-328. DOI: 10.1002/hon.3164_232.
11 Thieblemont, et al. Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial. Leukemia. 2024; 38: 2653–2662. DOI: 10.1038/s41375-024-02410-8.
12 Engelberts PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent T-cell-mediated killing of malignant B cells in preclinical models and provides opportunities for subcutaneous dosing. EBioMedicine. 2020;52:102625. DOI: 10.1016/j.ebiom.2019.102625.
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