Topline phase 3 data show epcoritamab plus R-CHOP reduced the risk of progression or death by 51% in newly diagnosed diffuse large B-cell lymphoma.
Adding the bispecific antibody epcoritamab to standard rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) reduced the risk of disease progression or death by 51% in newly diagnosed diffuse large B-cell lymphoma (DLBCL), according to topline phase 3 EPCORE DLBCL-2 results announced Oct. 5 by AbbVie and Genmab.1
Epcoritamab is approved only for relapsed or refractory lymphoma, so the companies said they will now engage regulators on next steps.1
"DLBCL is an aggressive disease and the need to advance treatment options is critical. These positive topline results suggest that epcoritamab combined with R-CHOP could offer a potential new standard of care in newly diagnosed DLBCL patients," said Daejin Abidoye, MD, Vice President, Therapeutic Area Head, Oncology, Solid Tumor and Hematology, AbbVie. "The findings further strengthen our understanding and potential of bispecifics across the lymphoma treatment landscape, as we work to address urgent needs in this patient population."1
EPCORE DLBCL-2 (NCT05578976) is a global, open-label, randomized phase 3 trial that began Feb. 8, 2023, and is ongoing.1 Patients with an International Prognostic Index (IPI) score of 2 to 5 were randomized 2:1 to fixed-duration subcutaneous epcoritamab plus R-CHOP for six cycles, then two cycles of epcoritamab alone, or to R-CHOP for six cycles, then two cycles of rituximab.1
The primary endpoint was progression-free survival in patients with an IPI score of 3 to 5; the key secondary endpoint was the same measure in all patients scoring 2 to 5.1 The companies reported a hazard ratio of 0.49 in both populations (95% confidence interval, 0.35-0.69 and 0.36-0.67, respectively; P<.0001).1
They described the combination's safety as generally well tolerated and consistent with the known profiles of epcoritamab and R-CHOP.1 At the first planned efficacy interim analysis, an independent data monitoring committee recommended unblinding the study.1
DLBCL is the most common non-Hodgkin lymphoma worldwide, accounting for about 25% to 30% of cases, with roughly 25,000 new U.S. diagnoses annually.1 It grows quickly and is more common in older adults. R-CHOP is the long-standing first-line regimen, yet some patients relapse or do not respond.2
"As an investigator with firsthand experience in both the landmark trial that established R-CHOP as a standard of care nearly 25 years ago and EPCORE DLBCL-2, it is particularly meaningful to see the potential benefit of bispecific antibody therapy in newly diagnosed diffuse large B-cell lymphoma," said Gilles Salles, MD, PhD, Chief of the Lymphoma Service and holder of the Steven A. Greenberg Chair at Memorial Sloan Kettering Cancer Center. "The 51% reduction in the risk of progression or death is clinically meaningful and highly relevant to everyday practice. These results have the potential to be practice-changing and could mark an important step forward in bringing the opportunity of cure to more patients."
The release notes that Salles has financial interests related to AbbVie and Genmab.1 The phase 3 POLARIX trial tested a different frontline approach, replacing vincristine with the antibody-drug conjugate polatuzumab vedotin; patients had a lower risk of progression, relapse or death than with R-CHOP in previously untreated intermediate- or high-risk DLBCL.3
Epcoritamab, co-developed by AbbVie and Genmab, is a subcutaneous bispecific antibody that binds CD3 on T cells and CD20 on B cells to direct T-cell killing of CD20-positive cells.1 Marketed as Epkinly in the U.S. and Japan and Tepkinly in the European Union, it is approved in certain lymphoma indications in more than 65 countries.1
U.S. use in relapsed or refractory DLBCL after two or more treatments rests on response data, with confirmatory studies ongoing; labeling warns of cytokine release syndrome and neurologic problems.1
The data are topline only, and the companies plan to submit them for presentation at a future medical meeting.1 The release does not report median progression-free survival, overall survival, response rates, or rates of cytokine release syndrome, neurologic events and infections with the combination.
Whether the progression-free survival gain extends to overall survival is unaddressed. That distinction has precedent: in EPCORE DLBCL-1, a phase 3 trial in relapsed or refractory DLBCL, overall survival was the sole U.S. primary endpoint and was not met, the companies clarified in July.4
Epcoritamab plus R-CHOP is investigational and not approved by regulatory authorities.1
"These topline results of epcoritamab in combination with R-CHOP mark the first Phase 3 study to demonstrate a statistically significant improvement in progression-free survival in patients with newly diagnosed DLBCL treated with a bispecific antibody combination and have the potential to reshape the frontline treatment landscape," said Jan van de Winkel, PhD, Chief Executive Officer of Genmab. "While treatment advances have improved outcomes for patients with diffuse large B-cell lymphoma, options for newly diagnosed patients remain limited, reinforcing the need for additional therapies that can treat as many patients as possible in the frontline setting."1
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