ABBV AbbVie Inc

• Data presented at the 66^th Annual Meeting and Exposition of the American Society of Hematology (ASH)

NORTH CHICAGO, Ill., Dec. 9, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new results from two ongoing clinical trials evaluating epcoritamab, a CD3xCD20 bispecific T-cell-engaging antibody administered subcutaneously, in adult patients with diffuse large B-cell lymphoma (DLBCL) at the 66^th 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 100% and a complete response (CR) rate of 87%. Among complete responders, an estimated 83% remained in remission after two years. Separately, three-year follow-up results from the Phase 2 EPCORE^® NHL-1 trial (Abstract #4480),²  evaluating epcoritamab monotherapy in challenging-to-treat adult patients (n=157) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy showed that among the 41% of patients who achieved a CR, an estimated 52% were still responding at three years (median CR duration: 36.1 months).

DLBCL is the most common type of non-Hodgkin's lymphoma (NHL) worldwide, accounting for approximately 25-30% of all NHL cases.^3,4 In the U.S., there are approximately 25,000 new cases of DLBCL diagnosed each year.⁵ 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.^6,7 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.^6,8

"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, 35% of patients (n=16) had bulky disease (>10 cm), and 21% (n=6/28) had double-hit/triple-hit DLBCL, which are aggressive subtypes caused by major genetic mutations.

A minimal residual disease (MRD) analysis from blood samples (n=33) showed that 91% of patients achieved MRD negativity, indicating no detectable disease as defined by ctDNA.¹⁰

The most common treatment-emergent adverse events (TEAEs) were neutropenia (70%), anemia (69%), cytokine release syndrome (CRS 60%), fatigue (49%), nausea (47%), pyrexia (42%), and injection-site reaction (40%). Four patients (9%) discontinued epcoritamab due to TEAEs; fatal TEAEs occurred in two patients (COVID-19 and septic shock). CRS events were mostly low grade (45% Grade 1, 11% Grade 2, 4% Grade 3) and mainly occurred after the first full dose. All CRS cases resolved, and none led to discontinuation. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in two patients (one Grade 1; one Grade 2) and resolved in a median of 2.5 days without leading to discontinuation.

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 was 41%. 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 (51%; 32% Grade 1, 16% Grade 2, 3% Grade 3), fatigue (25%), and pyrexia (25%); CRS rates remained unchanged since prior reports. Fatal TEAEs were reported in 20 patients; 10 patients had Grade 5 COVID-19 (including COVID-19 pneumonia). 73% of patients who received epcoritamab for two or more years did not experience a Grade 3 or higher infection after two years (median follow-up after two years: 12.3 months). Incidence of Grade 3 or higher cytopenias was highest (27%) during the first eight weeks of treatment and rates were within 0-13% in subsequent 12-week time periods up to week 144. Immunoglobulin G levels decreased by a median of ~20% after the start of epcoritamab treatment (baseline median, 540.0 mg/dL) and remained stable over time. 

"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 U.S. and Japan, and TEPKINLY in the EU) has received regulatory approval in certain lymphoma indications in several territories. Use of epcoritamab + R-CHOP in first-line DLBCL is not approved in the U.S. or in the EU or in any other territory. The safety and efficacy of epcoritamab for use as a combination therapy in DLBCL have not been established.

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 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 lenalidomide compared to chemotherapy infusion in patients with R/R DLBCL (NCT06508658). The safety and efficacy of epcoritamab have not been established for these investigational uses.

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:

• 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 the United States and Western Europe: Population-Level Projections for 2020-2025. Leuk Lymphoma. 2022;63(1):54-63. doi: 10.1080/10428194.2021.1975188.
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.

View original content to download multimedia:https://www.prnewswire.com/news-releases/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-302325678.html

SOURCE AbbVie