Genmab’s Phase III trial of a combination therapy including its bispecific T-cell engager (BiTE) combination, including Epkinly, has met its primary endpoint in adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
In the EPCORE DLBCL-4 trial (NCT06508658), Genmab investigated a combination of fixed-duration Epkinly (epcoritamab) and Bristol Myers Squibb’s (BMS’s) Revlimid (lenalidomide), compared to standard-of-care (SoC), rituximab plus gemcitabine plus oxaliplatin (R-GemOx), in DLBCL patients who received at least one prior line of treatment.
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Topline data shows the trial met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in progression-free survival (PFS).
The risk of disease progression and death was reduced by 60% and 56% based on different censoring rules in the US and outside the US, respectively.
The safety profile of the combo was consistent with the previously reported safety profiles of the individual agents.
Dr Jan van de Winkel, CEO of Genmab, said: “These topline results add to the growing evidence supporting the versatility of Epkinly-based combinations, including fixed-duration Epkinly, across lines of therapy for patients with DLBCL who received at least one prior treatment. With each new combination and treatment setting, we are building on our vision for Epkinly as a core therapy across B-cell malignancies. We look forward to engaging with regulatory authorities as we continue to advance this programme.”
Based on the Phase III topline data, Genmab and co-developer AbbVie will engage global regulatory authorities. Data will be submitted for presentation at a future medical meeting.
This data will be welcomed by investors as it follows a negative readout from the companies in the EPCORE DLBCL-1 trial. While Genmab and AbbVie said it was the first Phase III trial to show improved PFS in patients with r/r DLBCL who received CD3×CD20 T-cell engaging bispecific monotherapy, the goal of overall survival (OS) did not achieve statistical significance.
BiTE treatments growing considerably
BiTEs have a successful track record of receiving accelerated US Food and Drug Administration (FDA) approvals for hard-to-treat blood malignancies such as multiple myeloma. This includes Amgen’s Blincyto (blinatumomab), Johnson & Johnson’s (J&J’s) Tecvayli (teclistamab) and Pfizer’s Elrexfio (elranatamab), among others.
There has also been success with BiTEs in solid malignancies, with Amgen’s Imdelltra (tarlatamab-dlle) having received approval for extensive-stage small cell lung cancer (ES SCLC) in patients with disease progression on or after platinum-based chemotherapy, such as cisplatin and etoposide, which has dominated the treatment paradigm for decades.
There have, however, been some disappointments with BiTE therapies. In 2025, the FDA last year refused to approve Roche’s Columvi (glofitamab) in combination with GemOx, despite the Phase III trial of the combination showing an improvement in OS in second-line DLBCL.
Roche has another candidate in the mix, however, in Lunsumio (mosunetuzumab). In a Phase III trial, Lunsumio plus Polivy (polatuzumab vedotin) achieved a statistically significant improvement in PFS in second- or later-line DLBCL.
In 2023, BiTEs collectively generated $1.45bn in global sales. According to GlobalData, by 2030, this value is expected to increase 13-fold, where BiTEs are forecast to generate $20.6bn. J&J is estimated to dominate this drug category, with the two top-selling BiTEs, Tecvayli and Talvey, encompassing 40% of the total market.
GlobalData is the parent company of Clinical Trials Arena.
