AbbVie Presents Data at the 64th American Society of Hematology (ASH) Annual Meeting Evaluating Epcoritamab (DuoBody®-CD3xCD20) Across B-Cell Lymphomas

• Four oral presentations presented at ASH highlight data evaluating investigational epcoritamab for the treatment of relapsed/refractory (R/R) follicular lymphoma, previously untreated follicular lymphoma, R/R diffuse large B-cell lymphoma and Richter's syndrome

NORTH CHICAGO, Ill., Dec. 11, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced data from multiple clinical trials evaluating epcoritamab (DuoBody^®-CD3xCD20), an investigational subcutaneous bispecific antibody, alone or in combination for the treatment of patients with relapsed/refractory (R/R) follicular lymphoma (FL), previously untreated FL, R/R diffuse large B-cell lymphoma (DLBCL), as well as Richter's syndrome at the 64^th American Society of Hematology (ASH) Annual Meeting.

Notably, initial results of investigational epcoritamab in patients with R/R FL and previously untreated FL are featured during session 623 on Sunday, December 11 starting at 4:30 p.m. CST. The results are part of the EPCORE™ NHL-2 study, a Phase 1b/2, open-label trial to assess the safety and preliminary efficacy of epcoritamab in combination with other agents in patients with B-cell non-Hodgkin's lymphoma, including FL. Approximately 2.7 per 100,000 people in the U.S. are newly diagnosed with FL every year and the median age of patients at diagnoses with FL is 63.^1,2,3 FL is typically a slow-growing or indolent form of non-Hodgkin's lymphoma (NHL) that arises from B-lymphocytes.⁴ Although FL is a slow-growing lymphoma, it is considered incurable with conventional therapy.^5,6

"These data at this year's ASH meeting are promising as they support continued investigation of epcoritamab for patients in need of new treatment options for follicular lymphoma and other B-cell lymphomas," said Mohamed Zaki, M.D., Ph.D., vice president and head, global oncology development, AbbVie. "Along with Genmab, we look forward to continuing to build on our promise of exploring a potential core therapy for patients with B-cell malignancies in a variety of treatment settings."

Additional results from the EPCORE™ NHL-2 study as well as the EPCORE™ CLL-1 study were presented for investigational epcoritamab in R/R DLBCL and Richter's syndrome respectively. The EPCORE™ CLL-1 study is an open-label, multi-center, safety and efficacy trial of epcoritamab in R/R chronic lymphocytic leukemia (CLL) and Richter's syndrome. The trial consists of two parts, a dose escalation Phase (Phase Ib) and an expansion Phase (Phase II).⁷

Abstract #609: Subcutaneous Epcoritamab with Rituximab + Lenalidomide in Patients with Relapsed or Refractory Follicular Lymphoma: Phase 1/2 Trial Update

Oral Presentation: Sunday, December 11, 2022 at 5:00 p.m. CST

In the R/R FL arm of the EPCORE™ NHL-2 trial, 95 percent (63/66) of efficacy-evaluable patients treated with subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an overall response rate (ORR) and 80 percent (53/66) achieved complete metabolic response (CMR). The majority of patients achieved a response at first tumor response assessment and most continued to respond through the latest assessment at the time of data collection. 

A manageable cytokine release syndrome (CRS) occurrence was observed with only low-grade events, mainly following the first full dose, all of which resolved. The most common treatment-emergent adverse events (TEAEs) of any grade were neutropenia (47%), CRS (43%), injection-site reactions (32%), fatigue (31%), constipation (25%), COVID-19 (25%), pyrexia (25%) and infusion-related reaction (21%).

Abstract #611: Subcutaneous Epcoritamab in Combination with Rituximab + Lenalidomide for First-Line Treatment of Follicular Lymphoma: Initial Results from Phase 1/2 Trial

Oral Presentation: Sunday, December 11, 2022 at 5:30 p.m. CST

In the previously untreated FL patient arm of the EPCORE™ NHL-2 trial, 94 percent (34/36) of efficacy-evaluable patients who received subcutaneous epcoritamab in combination with rituximab and lenalidomide achieved an ORR, including 86 percent (31/36) achieving CMR as their best overall response. In the trial, the investigational combination therapy showed a manageable CRS occurrence with only low-grade events, all of which resolved. 

The most common TEAEs of any grade were CRS (54%), neutropenia (47%), pyrexia (44%), fatigue (37%), injection-site reaction (37%), headache (34%), COVID-19 (33%), diarrhea (32%), constipation (29%), rash (27%), increased alanine aminotransferase (ALT) (22%), and vomiting (22%). 

Abstract #443: Subcutaneous Epcoritamab + R-Dhax/C in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2 Results

Oral Presentation: Sunday, December 11, 2022 at 10:30 a.m. CST

Results from the EPCORE™ NHL-2 arm evaluating 27 patients with R/R DLBCL who were eligible for autologous stem cell transplant, showed an 85 percent (23/27) ORR and 67 percent (18/27) CMR following treatment with the combination of subcutaneous epcoritamab plus standard rituximab, dexamethasone, cytarabine, and oxaliplatin or carboplatin (R-DHAX/C) salvage therapy.

The most common TEAEs of any grade were thrombocytopenia (69%), anemia (51%), neutropenia (44%), CRS (41%), nausea (31%), fatigue (28%), constipation (24%), diarrhea (24%), headache (24%), pyrexia (24%) and increased aspartate aminotransferase (AST) (21%). All CRS events were low-grade and resolved. 

Abstract #348: Subcutaneous Epcoritamab in Patients with Richter's Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1)

Oral Presentation: Saturday, December 10, 2022 at 5:15 p.m. CST

Preliminary results from the EPCORE™ CLL-1 trial showed that treatment with subcutaneous epcoritamab monotherapy had promising antitumor activity in 10 patients with Richter's syndrome, with a 60 percent ORR and a 50 percent CMR rate. Most responses were observed by the first assessment at week six. In the trial, patients experienced only low-grade CRS events, mostly associated with the first full dose, all of which resolved. 

The most common TEAEs of any grade were CRS (90%), anemia (50%), neutropenia (50%), injection-site reaction (40%), thrombocytopenia (40%), hypophosphatemia (30%), Hypokalemia (30%), hyperglycemia (30%), COVID-19 (30%), diarrhea (30%), fatigue (30%), and nausea (30%).

About Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is a fast-growing type of NHL that affects B-cell lymphocytes, a type of white blood cell.⁸ It is the most common type of NHL worldwide and accounts for approximately 30 percent of all NHL cases.⁸ DLBCL can arise in lymph nodes, as well as in organs outside of the lymphatic system.⁸ The disease occurs more commonly in the elderly and is slightly more prevalent in men.⁸

About Richter's Syndrome
Richter's syndrome, also known as Richter's transformation, is defined as the transformation of CLL into an aggressive lymphoma, most commonly DLBCL.^9,10 Richter's syndrome occurs in approximately 2 percent to 10 percent of CLL patients during the course of their disease.⁹

About the EPCORE™ NHL-2 Trial
EPCORE™ NHL-2 is a Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard-of-care agents in subjects with B-cell non-Hodgkin's lymphoma. The trial consists of two parts: Part 1 (Dose Escalation) and Part 2 (Dose Expansion).¹¹

The primary objective of Part 1 is safety, and it includes Arm 1–5. Part 2 includes all 8 arms (Arm 1–8) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Patients in Arm 1–5 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities will be assessed in Part 1 and for a selected number of patients in Arm 8 during a 28-day period (safety-run Phase). The arms are conducted in parallel.¹¹

About Epcoritamab
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab's proprietary DuoBody technology. 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 CD20 is expressed on B-cells and a clinically validated therapeutic target in many B-cell malignancies, including DLBCL, FL, mantle cell lymphoma and CLL.^13,14 

AbbVie recently announced that the Biologics License Application (BLA) for epcoritamab for the treatment of adult patients with R/R large B-cell lymphoma after two or more lines of systemic therapy was accepted for priority review by the U.S. Food and Drug Administration. Additionally, the European Medicines Agency has validated a Marketing Authorization Application for epcoritamab for the treatment of adult patients with R/R DLBCL after two or more lines of systemic therapy.

Epcoritamab is being co-developed by AbbVie and Genmab 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. The companies are committed to evaluating 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) and a Phase 3, open-label clinical trial evaluating epcoritamab in combination in patients with R/R FL (NCT: 05409066). 

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 and our Blood Cancer Press Kit page.

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, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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, among others, 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 indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, failure to realize the expected benefits from AbbVie's acquisition of Allergan plc ("Allergan"), failure to promptly and effectively integrate Allergan's businesses, competition from other products, challenges to intellectual property, difficulties inherent in the research and development process, adverse litigation or government action, changes to laws and regulations applicable to our industry and the impact of public health outbreaks, epidemics or pandemics, such as COVID-19. 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 2021 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 to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

¹ National Institutes of Health official website: SEER Cancer Statistics. https://seer.cancer.gov/csr/1975_2017/. Table 19.29. Accessed November 2022.
² Cancer Stat Facts: Follicular Lymphoma. https://seer.cancer.gov/statfacts/html/follicular.html. Accessed November 2022
³ SEER Cancer Statistics. https://seer.cancer.gov/csr/1975_2017/. Table 19.26. Accessed November 2022.
⁴ Lymphoma Research Foundation official website. https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed November 2022.
⁵ Link BK, 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.
⁶ Ren J, et al. 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.
⁷ Safety & Efficacy Study of Epcoritamab in subjects with R/R chronic lymphocytic leukemia and richter's syndrome. ClinicalTrials.gov. (n.d.). Accessed November 2022, from https://clinicaltrials.gov/ct2/show/NCT04623541
⁸ Sehn, Salles. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384:842-858. DOI: 10.1056/NEJMra2027612.
⁹ Richter's syndrome. Leukaemia Foundation. (2022, October 5). Accessed November 2022, from https://www.leukaemia.org.au/blood-cancer-information/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/richters-syndrome/#:~:text=Richter's%20Syndrome%20(RS)%2C%20also,form%20of%20large%20cell%20lymphoma.
¹⁰ Parikh SA, Kay NE, Shanafelt TD. How we treat Richter syndrome. Blood. 2014 Mar 13;123(11):1647-57. doi: 10.1182/blood-2013-11-516229. Epub 2014 Jan 13. PMID: 24421328; PMCID: PMC3954047.
¹¹ Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL). ClinicalTrials.gov. (n.d.). Accessed November 2022, from https://clinicaltrials.gov/ct2/show/NCT04663347
¹² Engelberts 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.
¹³ Rafiq, Butchar, Cheney, et al. "Comparative Assessment of Clinically Utilized CD20-Directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and Macrophage Properties." J. Immunol. 2013;190(6):2702-2711. DOI: 10.4049/jimmunol.1202588.
¹⁴ Singh, Gupta, Almasan. "Development of Novel Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on Cell Surface: Looking to Improve Immunotherapy Response." J Cancer Sci Ther. 2015;7(11):347-358. DOI: 10.4172/1948-5956.1000373.

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