Clinical trial results can be a mixed bag, and Genmab A/S (GMAB) delivered exactly that on Friday. The Danish biotech released topline data from its Phase 3 EPCORE DLBCL-1 trial testing epcoritamab in diffuse large B-cell lymphoma (DLBCL), and while the drug showed real benefits, it missed the study's most important target: overall survival.
The trial pitted epcoritamab against standard chemotherapy options—specifically, investigator's choice of either rituximab plus gemcitabine plus oxaliplatin (R-GemOx), or bendamustine plus rituximab (BR)—in patients with relapsed or refractory DLBCL. This global study enrolled 483 patients who had already been through at least one prior treatment and weren't candidates for high-dose chemotherapy followed by stem cell transplant. The trial kicked off in January 2021 and is still ongoing.
What the Data Showed
The headline number wasn't what Genmab hoped for: overall survival came in at a hazard ratio of 0.96, which failed to reach statistical significance. In clinical trial language, that means the study didn't prove epcoritamab helps patients live longer than the comparison treatments.
But here's where it gets more interesting. The T-cell-engaging bispecific antibody, delivered subcutaneously, actually demonstrated improvement in progression-free survival—meaning it kept the disease from getting worse for longer periods. On top of that, patients treated with epcoritamab monotherapy showed better complete response rates, their responses lasted longer, and they went longer before needing another treatment.
The safety profile looked consistent with what's already known about epcoritamab, with no unexpected adverse events popping up. Genmab noted they're still digging into the data, including potential confounding factors like the COVID-19 pandemic and the increasing availability of newer anti-lymphoma therapies that might have influenced outcomes.
Where Things Go From Here
The complete trial results will be presented at an upcoming medical conference. Genmab and its partner AbbVie Inc. (ABBV) plan to meet with global regulatory authorities to figure out next steps.
Looking ahead, Genmab expects data from two Phase 3 trials evaluating fixed-duration epcoritamab for DLBCL in 2026. The drug is already on the market under accelerated approval—sold as Epkinly in the U.S. and Japan, and as Tepkinly in the European Union.
The Analyst's Take
William Blair acknowledged the OS miss is disappointing and has investors wondering whether Epkinly's current accelerated approval for relapsed/refractory DLBCL might be in jeopardy.
But analyst Matt Phipps isn't hitting the panic button. He points to strong Phase 2 results combining Epkinly with R-CHOP, which gives him confidence in the frontline EPCORE DLBCL-2 trial reading out in 2026. That trial could support expansion into the largest segment of the DLBCL market.
With multiple pivotal readouts coming in 2026 across Epkinly, Rina-S, and petosemtamab, Phipps believes Genmab has significant upside potential and maintains an Outperform rating.
"We believe it is unlikely Epkinly would lose accelerated approval in DLBCL, given that Columvi still has an accelerated approval despite receiving a complete response letter from the FDA for the confirmatory STARGLO trial, and ongoing Phase 3 trials have the potential to provide confirmatory evidence for Epkinly," Phipps wrote.
For context, Columvi (glofitamab) is a bispecific antibody medicine from Roche Holdings AG (RHHBY) that faced its own regulatory speed bump but maintained its approval.
Genmab shares were down 2.36% at $31.49 at the time of publication on Tuesday.
