On December 11, 2022 AbbVie (NYSE: ABBV) reported 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 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, AbbVie, DEC 11, 2022, View Source [SID1234625009]).

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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 (Free ASH Whitepaper) 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).