AbbVie and Genmab Announce Positive Topline Results from Phase 1/2 EPCORE™ NHL-1 Trial Evaluating Epcoritamab (DuoBody®-CD3xCD20) in Patients with Relapsed/Refractory Follicular Lymphoma (FL)

-  Based on the topline results of epcoritamab from the EPCORE™ NHL-1 clinical trial, AbbVie and Genmab will engage global regulatory authorities to discuss next steps

-  Additional data from the clinical trial will be presented at a future medical meeting

-  Follicular lymphoma is a common form of non-Hodgkin's lymphoma and currently has limited treatment options, particularly in the relapsed/refractory setting 

NORTH CHICAGO, Ill., June 27, 2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) and Genmab (Nasdaq: GMAB) today announced topline results from the follicular lymphoma (FL) cohort of the Phase 1/2 EPCORE™ NHL-1 clinical trial evaluating epcoritamab (DuoBody^®-CD3xCD20), an investigational T-cell engaging bispecific antibody administered subcutaneously. The study cohort includes 128 adult patients with relapsed or refractory (R/R) FL who received at least two or more lines of systemic therapy. 70.3 percent of patients were double refractory to an anti-CD20 monoclonal antibody and an alkylating agent. Epcoritamab is being co-developed by AbbVie and Genmab as part of the companies' oncology collaboration.

"We are encouraged by these topline results, which further support the clinical profile of epcoritamab as a potential therapeutic option for patients with relapsed or refractory follicular lymphoma," said Mariana Cota Stirner, M.D., Ph.D., vice president, therapeutic area head for hematology, AbbVie. "Together with our partner Genmab, these results may bring us one step closer to our goal of advancing a potential core therapy for patients with B-cell malignancies."

EPCORE™ NHL-1 is an open-label trial evaluating the safety and preliminary efficacy of epcoritamab and consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a optimization part. The topline results from this cohort showed an overall response rate (ORR) of 82 percent as confirmed by an independent review committee (IRC), which exceeded the protocol prespecified threshold for efficacy. The observed median duration of response (DOR) was not reached, and longer follow-up will be required. The median number of lines of prior therapy in this cohort was three (range: two to four lines of therapy).

No new safety signals were observed with epcoritamab in this study at the time of this analysis. The most common treatment-emergent adverse event was cytokine release syndrome (CRS) with 66.4 percent (1.6 percent Grade 3 or higher). The optimization part of the trial is continuing to evaluate alternative step-up dosing regimens to help further mitigate the risk of CRS, preliminary data are encouraging.

Full results from the study will be submitted for presentation at a future medical meeting.

About the Phase 1/2 EPCORE™ NHL-1 trial
EPCORE™ NHL-1 is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab that consists of three parts: a Phase 1 first-in-human, dose escalation part; a Phase 2a expansion part; and a Phase 2a dose optimization part. The trial was designed to evaluate subcutaneous epcoritamab in adult patients with relapsed, progressive or refractory CD20+ mature B-cell non-Hodgkin's lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a expansion part, additional patients are being enrolled to further explore the safety and efficacy of epcoritamab in three cohorts of patients with different types of relapsed or refractory (R/R) B-cell NHLs who have limited therapeutic options. The dose optimization part evaluates the potential for alternative step-up dosing regimens to help further minimize Grade 2 CRS and mitigate Grade ≥3 cytokine release syndrome. The primary endpoint of the expansion part was overall response rate as assessed by an independent review committee. Secondary efficacy endpoints included duration of response, complete response rate, duration of complete response, progression-free survival, and time to response as determined by the Lugano criteria. Overall survival, time to next therapy, and rate of minimal residual disease negativity were evaluated as secondary efficacy endpoints.

About Follicular Lymphoma 
Follicular lymphoma (FL) is typically an indolent, or slow growing, form of NHL that arises from B-cell lymphocytes.¹ FL is the second most common form of NHL overall, accounting for 20 to 30 percent of all NHL cases, and representing 10 to 20 percent of all lymphomas in the western world.^2,3 Although FL is an indolent lymphoma, it is considered incurable with conventional therapy.^4,5

About Epcoritamab 
Epcoritamab is an investigational 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.⁶ 

Epcoritamab-bysp (EPKINLY™) was recently approved in the United States (U.S.) and is indicated for the treatment of adult patients with R/R diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), including DLBCL arising from indolent lymphoma, and high-grade B-cell lymphoma (HGBL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).  Please see U.S. Important Safety Information below.

In October 2022, a Marketing Authorization Application was submitted for epcoritamab for the treatment of patients with R/R DLBCL after two or more lines of systemic therapy, which was validated by the European Medicines Agency. Additionally, in December 2022, a Japan new drug application was submitted to the Ministry of Health, Labor and Welfare of Japan for epcoritamab for the treatment of patients with R/R large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. Epcoritamab is not approved in the European Union and Japan.

The companies will share commercial responsibilities in the United States and Japan, with AbbVie responsible for further global commercialization. AbbVie will continue to pursue regulatory submissions for epcoritamab across international markets excluding the United States and Japan throughout the year.

Genmab and AbbVie are continuing to evaluate the use of epcoritamab as a monotherapy, and in combination, across lines of therapy in a range of hematologic malignancies. This includes an ongoing Phase 3, open-label, randomized trial evaluating epcoritamab as a monotherapy in patients with R/R DLBCL (NCT: 04628494), an ongoing Phase 3, open-label, randomized trial evaluating epcoritamab in combination in adult participants with newly diagnosed DLBCL (NCT: 05578976), and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat newly diagnosed patients with DLBCL or FL. The safety and efficacy of epcoritamab has not been established for these investigational uses. Please visit clinicaltrials.gov for more information.

EPKINLY™ (epcoritamab-bysp) U.S. IMPORTANT SAFETY INFORMATION

Important Warnings—EPKINLY can cause serious side effects, including:

• Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop symptoms of CRS, including fever of 100.4°F (38°C) or higher, dizziness or lightheadedness, trouble breathing, chills, fast heartbeat, feeling anxious, headache, confusion, shaking (tremors), or problems with balance and movement, such as trouble walking.
  
  Due to the risk of CRS, you will receive EPKINLY on a "step-up" dosing schedule. The step-up dosing schedule is when you receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of your first cycle of treatment (cycle 1). You will receive your first full dose of EPKINLY on day 15 of cycle 1. If your dose of EPKINLY is delayed for any reason, you may need to repeat the step-up dosing schedule. Before each dose in cycle 1, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of CRS with future cycles.
   
• Neurologic problems. EPKINLY can cause serious neurologic problems that can be life-threatening and lead to death. Neurologic problems may happen days or weeks after you receive EPKINLY. Your healthcare provider may refer you to a healthcare provider who specializes in neurologic problems. Tell your healthcare provider right away if you develop any symptoms of neurologic problems, including trouble speaking or writing, confusion and disorientation, drowsiness, tiredness or lack of energy, muscle weakness, shaking (tremors), seizures, or memory loss.

Due to the risk of CRS and neurologic problems, you should be hospitalized for 24 hours after receiving your first full dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will monitor you for symptoms of CRS and neurologic problems during treatment with EPKINLY, as well as other side effects, and treat you if needed. Your healthcare provider may temporarily stop or completely stop your treatment with EPKINLY if you develop CRS, neurologic problems, or any other side effects that are severe.

Do not drive or use heavy or potentially dangerous machinery if you develop dizziness, confusion, tremors, drowsiness, or any other symptoms that impair consciousness until your symptoms go away. These may be symptoms of CRS or neurologic problems.

EPKINLY can also cause other serious side effects, including:

• Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for symptoms of infection before and during treatment. 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. Low blood cell counts are common during treatment with EPKINLY and 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 cell counts (neutropenia), which can increase your risk for infection; low red blood cell counts (anemia), which can cause tiredness and shortness of breath; and low platelet counts (thrombocytopenia), which can cause bruising or bleeding problems.

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 of your medical conditions, including if you:

• have an infection.
• are pregnant or plan to become pregnant. EPKINLY may harm your unborn baby. Females who are able to become pregnant: Your healthcare provider should do a pregnancy test before you start treatment with EPKINLY. 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.
• are breastfeeding or plan to breastfeed. It is not known if EPKINLY passes into your breast milk. Do not breastfeed during treatment with EPKINLY and for 4 months after your last dose of EPKINLY.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

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.

These are not all 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 the Full Prescribing Information and Medication Guide, including Important Warnings.

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 https://www.abbvie.com/oncology.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines 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, eye care, virology and gastroenterology, in addition to products and services across our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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 2022 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.

¹ What is Lymphoma. Lymphoma Research Foundation. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed June 22, 2023.
² Ma S. Risk factors of follicular lymphoma. Expert Opin Med Diagn. 2012;6:323–33. DOI: 10.1517/17530059.2012.686996.
³ Luminari S, Bellei M, Biasoli I, et al. Follicular lymphoma—treatment and prognostic factors. Rev Bras Hematol Hemoter. 2012;34:54–9. DOI: 10.5581/1516-8484.20120015.
⁴ Link BK, Day BM, Zhou X, et al. Second-Line and Subsequent Therapy and Outcomes for Follicular Lymphoma in the United States: Data From the Observational National LymphoCare Study. Br J Haematol. 2019;184(4):660-663. DOI: 10.1111/bjh.15149.
⁵ Ren J, Asche CV, Shou Y, Galaznik A. Economic Burden and Treatment Patterns for Patients With Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the USA. J Comp Eff Res. 2019;8(6):393-402. DOI: 10.2217/cer-2018-0094.
⁶ 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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